Bases Moleculares Del Desarrollo Embrionario 1
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BASES MOLECULARES DEL DESARROLLO EMBRIONARIO
Lagman 2010
Estructura del ADNLa cromatina es: ADN + protenas
Esta !orma"a por n#c$eosomas% E$ n#c$eosoma est& !orma"o por #n oct&mero "e
protenas 'istonas + 1(0 pares "e )ases%Los n#c$eosomas est&n #ni"os por ADN * otras protenas 'istonas $$ama"as 1
E$ ADN est& enro$$a"o, as enro$$a"o no se p#e"e transcri)ir, se $$ama 'eterocromatina%
E$ ADN "esenro$$a"o se $$ama e#cromatina
GenesUn gen est& comp#esto por e-ones .se sinteti/an $as protenas e intrones !orma"os por
so$o ADN #e no !orma protenas%
Regin promotora: sitio "on"e se #ne $a ARN po$imerasa
3#nto "e inicio "e $a transcripcin
3#nto "e inicio "e $a tra"#ccin: "on"e se #)ica e$ primer amino&ci"o "e $a protenaCo"n "e para"a "e $a tra"#ccin
Regin 45: $#gar "e insercin "e $a po$i .A% s# !#ncin es esta)i$i/ar e$ ARN * $e
permite sa$ir "e$ n6c$eo
7ranscripcin: proce"e "e$ e-tremo 85'acia e$ e-tremo 49
Regin "on"e se #ne $a ARN po$imerasa
Contiene $a porcin $$ama"a 7A7A
Caa 7A7A
3ara po"er #nir $a ARN po$imerasa a esta /ona se re#iere "e protenas $$ama"as
;acin .#e acti>a o in'i)e $a transcripcin "e$ gen
Como res#$ta"o e$ ADN se "esenro$$a
3otencia"ores
E$ementos reg#$a"ores
Resi"en en c#a$#ier parte "e $a mo$?c#$a "e ADN
Los potencia"ores se #nen a !actor "e transcripcin, esto para reg#$ar $a
>e$oci"a" * e!iciencia "e $a e-presin "e$ gen%
a* "i!erentes potencia"ores "e$ mismo gen en "i!erentes tei"os% 3or eemp$o3A@ #n !actor "e transcripcin tiene 4 potencia"ores "istintos: en e$ p&ncreas
#n potencia"or, en e$ oo #no "istinto, en e$ t#)o ne#ra$ otro "istinto
Los $$ama"os si$encia"ores son potencia"ores #e in'i)en $a transcripcin%
Un potencia"or acti>a #n gen * si$encia a otro%
ARN n#c$ear: es m&s $argo, contiene intrones
Desenpa$me: se e$iminan intrones%
Empa$me a$ternati>o: se sinteti/an "i!erentes protenas a partir "e #n mismo gen a$
e$iminar "i!erentes intrones, $os e-ones se empa$man "e "i!erente manera% Esto $o 'acen
$os enpa$mosomas #e son comp$eos ARN protena%
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Iso!ormas "e empa$me: protenas #e "eri>an "e #n mismo gen% Eemp$o iso!ormas "e$
gen 71%
Una >e/ !orma"as $as protenas a s# >e/ p#e"en ser mo"i!ica"as * se a$tera s# !#ncin,
son mo"i!icaciones postrans"#cciona$es%
ersas >as "e sea$i/acin como angiog?nesis, crecimiento "e $os
a-ones * "i!erenciacin "e$ meso"ermo
2 3rotenas 'e"ge'og
Se $$aman as por#e co"i!ican #n patrn "e p#as en $as patas "e Drosop'i$a #e
rec#er"a $a !orma "e #n eri/o%
a* 4 genes 'e"ge'og
Desert
In"ian
Sonic 'e"ge'og
S# receptor es $$ama"o 3atc'e" #e se #ne a $a protena $$ama"a Smoot'ene"%
La protena Smoot'ene" trans"#ce $a sea$ "e 'e"ge'og, pero est& in'i)i"a pore$ 3atc'e" 'asta #e $a protena 'e"ge'og se #ne a s# receptor%
La !#ncin "e 'e"ge'og es p#es "esin'i)ir #n trans"#ctor #e norma$mente
estara acti>o%
4 3rotenas N7
Como mnimo e-isten 18 genes N7 "istintos%
S#s Receptores pertenecen a $a !ami$ia "e protenas !ri//$e"% .risa"o
3articipan en $a reg#$acin "e$ "iseo "e $as e-tremi"a"es, e$ "esarro$$o "e$
mesenc?!a$o * a$g#nos aspectos "e $a "i!erenciacin "e $os somitas * "e $as
estr#ct#ras #rogenita$es%
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( La s#per!ami$ia "e$ !actor "e trans!ormacin "e$ crecimiento )eta
Est& !orma"a por m&s "e 40 miem)ros, entre $os c#a$es se enc#entran:
e a ca)o se re#iere contacto estrec'o entre $os tei"os
in>o$#cra"os, si est&n m#* separa"os e$ proceso no oc#rre%
Car$son 2008
E$ mismo gen p#e"e act#ar en pero"os "istintos * en $a !ormacin "e "i!erente rgano%
As se re"#ce e$ n6mero "e mo$?c#$as necesarias para e$ contro$ "e$ "esarro$$o%
Esta &rea es "e m#c'o inter?s en $a in>estigacin onco$gica%
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Ca"a >e/ e-isten m&s pr#e)as "e #e e$ p$an "e "esarro$$o "e $os em)riones "e
mam!eros est& contro$a"o por m#c'os "e $os mismos genes #e 'an si"o i"enti!ica"os
en Drosop'i$a%
Las molculas que participan en el desarrollo se pueden agrupar en:
I- Factores de transcripcinII- Molculas de sealiacinIII- !eceptoresI"- #ransduccin de la sealI"- Acido retinoicoI"- Molculas de ad$esin
I- FA%#&!E' DE #!AN'%!I(%I&N: estos son protenas con "ominios #e se #nena$ ADN "e genes espec!icos% A"em&s poseen #na regin #e interact6a con $a
po$imerasa II "e$ ARN, o con otros !actores "e transcripcin , as se reg#$a $a canti"a"
"e ARN #e pro"#ce e$ gen% A$g#nos "e e$$os son genera$es es "ecir #e e-isten en casi
to"as $as c?$#$as "e$ organismo, otros son espec!icos "e ciertos tipos ce$#$ares o "ecierta !ase "e$ "esarro$$o%
Mechanism
Transcription factors bind to eitherenhanceror promoterregions of DNA adjacent to the genes
that they regulate. Depending on the transcription factor, the transcription of the adjacent gene
is either up- or down-regulated. Transcription factors use a variety of mechanisms for the
regulation of gene expression.!"#These mechanisms include$
stabili%e or bloc& the binding of 'NA polymerase to DNA cataly%e the acetylationor deacetylation of histoneproteins. The transcription factor can
either do this directly or recruit other proteins with this catalytic activity. (any
transcription factors use one or the other of two opposing mechanisms to regulate
transcription$ !)#
histone acetyltransferase*+AT activity acetylates histoneproteins, which wea&ens
the association of DNA withhistones, which ma&e the DNA more accessible to
transcription, thereby up-regulating transcription
histone deacetylase*+DA activity deacetylateshistoneproteins, which strengthens
the association of DNA with histones, which ma&e the DNA less accessible totranscription, thereby down-regulating transcription
recruit coactivatororcorepressorproteins to the transcription factor DNA complex!/#
Los )actores de transcripcin son:1 Genes que contienen $omeoca*a
7oma"o "e Moore octa>a e"icin
Las protenas pro"#ci"as contienen #n 'omeo"ominio a$tamente conser>a"o%+omeobox genes are critical in the establishment of body axes during embryogenesis.
http://en.wikipedia.org/wiki/Enhancer_(genetics)http://en.wikipedia.org/wiki/Enhancer_(genetics)http://en.wikipedia.org/wiki/Enhancer_(genetics)http://en.wikipedia.org/wiki/Promoter_(biology)http://en.wikipedia.org/wiki/Transcription_factor#cite_note-pmid11758455-12http://en.wikipedia.org/wiki/Acetylationhttp://en.wikipedia.org/wiki/Histonehttp://en.wikipedia.org/wiki/Transcription_factor#cite_note-pmid11909519-13http://en.wikipedia.org/wiki/Histone_acetyltransferasehttp://en.wikipedia.org/wiki/Histone_acetyltransferasehttp://en.wikipedia.org/wiki/Histonehttp://en.wikipedia.org/wiki/Histonehttp://en.wikipedia.org/wiki/Histonehttp://en.wikipedia.org/wiki/Histonehttp://en.wikipedia.org/wiki/Histone_deacetylasehttp://en.wikipedia.org/wiki/Histone_deacetylasehttp://en.wikipedia.org/wiki/Histonehttp://en.wikipedia.org/wiki/Histonehttp://en.wikipedia.org/wiki/Coactivator_(genetics)http://en.wikipedia.org/wiki/Corepressor_(genetics)http://en.wikipedia.org/wiki/Corepressor_(genetics)http://en.wikipedia.org/wiki/Corepressor_(genetics)http://en.wikipedia.org/wiki/Transcription_factor#cite_note-pmid10322133-14http://en.wikipedia.org/wiki/Embryogenesishttp://en.wikipedia.org/wiki/Enhancer_(genetics)http://en.wikipedia.org/wiki/Promoter_(biology)http://en.wikipedia.org/wiki/Transcription_factor#cite_note-pmid11758455-12http://en.wikipedia.org/wiki/Acetylationhttp://en.wikipedia.org/wiki/Histonehttp://en.wikipedia.org/wiki/Transcription_factor#cite_note-pmid11909519-13http://en.wikipedia.org/wiki/Histone_acetyltransferasehttp://en.wikipedia.org/wiki/Histonehttp://en.wikipedia.org/wiki/Histonehttp://en.wikipedia.org/wiki/Histone_deacetylasehttp://en.wikipedia.org/wiki/Histonehttp://en.wikipedia.org/wiki/Coactivator_(genetics)http://en.wikipedia.org/wiki/Corepressor_(genetics)http://en.wikipedia.org/wiki/Transcription_factor#cite_note-pmid10322133-14http://en.wikipedia.org/wiki/Embryogenesis -
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A- Genes +&,7o"os $os genes O@ contienen #na sec#encia "e 1G0 pares "e )ases, a esto se
$e "enomina $omeoca*a, .'omeosec#encia, #e co"i!ica #n $omeodominio"e0 amino&ci"os !orma"o por tres '?$ices a$!a% La tercera '?$ice se #ne a sitios
ADN #e contienen #no o m&s moti>os "e #nin tetran#c$eti"o 7AA7HA77A en
$os promotores "e $os genes "iana%
La protena pro"#ci"a contiene #n 'omeo"ominio constit#i"o por 0
amino&ci"os, #e es "e$ tipo '?$ice $a/o '?$ice%
En e$ ser '#mano est&n conser>a"os tam)i?n e$ or"en "e $os genes o- a $o
$argo "e$ ee anteroposterior * $a $oca$i/acin cromosmica%
Se $es "enomina O@ en '#manos * o- en >erte)ra"os%
En $os >erte)ra"os tienen #e >er con $a segmentacin craneoca#"a$
Los genes son acti>a"os * e-presa"os en $a "ireccin 45 85% .4 prima, 8
prima
Los genes 45se e-presan m&s temprano * m&s anteriormente%
S# reg#$acin: comp$ea
En >erte)ra"os 'a*: o-a, o-), o-c, o-"%
E$ ratn * e$ ser '#mano contienen a$ menos 4 genes 'omeocaa #)ica"os en (
cromosomas "i!erentes% En Drosop'i$a son G genes%
Se >e $a act#acin "e $os genes o- en e$ ee principa$ "e$ c#erpo, intestino, $os
miem)ros, $as c?$#$as sang#neas * $os genita$es internos * e-ternos%
7oma"o "e Langman 2010: As, $os genes #e "eterminan estr#ct#ras m&s
cranea$es se enc#entran en e$ e-tremo45"e$ ADN * se e-presan $os primeros,
mientras #e $os genes #e contro$an e$ "esarro$$o posterior se e-presan
consec#ti>amente * se "isponen "e !orma sec#encia$ 'acia e$ e-tremo 85% Estos
genes se conser>an en e$ ser '#mano en c#arto copias, O@A, O@B, O@C
* O@D, #e se "isponen * se e-presan como $o 'acen $os "e Drosop'i$a% 3or
tanto, ca"a gr#po se enc#entra en #n cromosoma "istinto * $os genes "e ca"agr#po se n#meran "e$ 1 a$ 14% Los genes con e$ mismo n6mero #e pertenecen a
gr#pos "istintos !orman #n gr#po par&$ogo como O@A(, O@B(, O@C( *
O@D(% E$ patrn "e e-presin "e estos genes, #nto con $os "atos aporta"os
por e-perimentos rea$i/a"os en ratones con genes inacti>a"os .JnocJo#t #e
carecen "e #no o m&s "e estos genes, apo*an $a 'iptesis "e #e estos genes
participan en el estalecimiento del e*e craneocaudal de los deri.ados de las/ capas germinati.as0
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name chromosome gene
+01A *or
sometimes
+01!
-HOXA@
chromosome 2+01A!,+01A",+01A),+01A/,+01A3,+01A4,+01A2,+01A5,
+01A!6,+01A!!,+01A!)
+017
- HOXB@chromosome !2
+017!,+017",+017),+017/,+0173,+0174,+0172,
+0178,+0175,+017!)
+01
- HOXC@chromosome !"
+01/,+013,+014,+018,+015, +01!6, +01!!,
+01!",+01!)
+01D
- HOXD@chromosome "
+01D!,+01D),+01D/,+01D8,+01D5, +01D!6,
+01D!!, +01D!",+01D!)
1- Genes (a2 3(aired o24La !ami$ia g?nica 3a-: miem)ros%
Las protenas 3a- contienen #n "ominio par "e 12G amino&ci"os, #e se #ne a$
ADN
Desempean !#nciones importantes en $os rganos "e $os senti"os * e$ sistema
ner>ioso
Paired box (Pax) genesare a family of tissue specific transcriptionfactorscontaining a paired domain and usually a partial or completehomeodomain. An octapeptidemay also be present. 9ax proteinsare importantin early animal development for the specification of specific tissues, as well asduring epimorphic limb regeneration in animals capable of such.
MIEMBROS
9A1!has been identified in mice with the development of vertebrate and
embryo segmentation, and some evidence this is also true in humans. :t
transcribes a //6 amino acidprotein from / exonsand !,)")bps in humans.
9A1"has been identified with &idneyand optic nerve development. :t
transcribes a /!2 amino acid protein from !! exons and /,"4! bps in
humans. (utation of 9A1" in humans has been associated with renal-coloboma syndromeas well as oligomeganephronia.!#
http://en.wikipedia.org/wiki/Chromosomehttp://www.genenames.org/data/hgnc_data.php?match=HOXA@http://en.wikipedia.org/wiki/Chromosome_7_(human)http://en.wikipedia.org/wiki/Homeobox_A1http://en.wikipedia.org/wiki/Homeobox_A1http://en.wikipedia.org/wiki/HOXA2http://en.wikipedia.org/wiki/HOXA3http://en.wikipedia.org/wiki/HOXA3http://en.wikipedia.org/wiki/HOXA3http://en.wikipedia.org/wiki/HOXA4http://en.wikipedia.org/wiki/HOXA5http://en.wikipedia.org/wiki/HOXA5http://en.wikipedia.org/wiki/HOXA5http://en.wikipedia.org/wiki/HOXA6http://en.wikipedia.org/wiki/HOXA7http://en.wikipedia.org/wiki/HOXA7http://en.wikipedia.org/wiki/HOXA7http://en.wikipedia.org/wiki/HOXA9http://en.wikipedia.org/wiki/HOXA10http://en.wikipedia.org/wiki/HOXA11http://en.wikipedia.org/wiki/HOXA11http://en.wikipedia.org/wiki/HOXA13http://www.genenames.org/data/hgnc_data.php?match=HOXB@http://en.wikipedia.org/wiki/Chromosome_17http://en.wikipedia.org/wiki/HOXB1http://en.wikipedia.org/wiki/HOXB1http://en.wikipedia.org/wiki/HOXB2http://en.wikipedia.org/wiki/HOXB3http://en.wikipedia.org/wiki/HOXB3http://en.wikipedia.org/wiki/HOXB3http://en.wikipedia.org/wiki/HOXB4http://en.wikipedia.org/wiki/HOXB5http://en.wikipedia.org/wiki/HOXB5http://en.wikipedia.org/wiki/HOXB5http://en.wikipedia.org/wiki/HOXB6http://en.wikipedia.org/wiki/HOXB7http://en.wikipedia.org/wiki/HOXB7http://en.wikipedia.org/wiki/HOXB7http://en.wikipedia.org/wiki/HOXB8http://en.wikipedia.org/wiki/HOXB8http://en.wikipedia.org/wiki/HOXB9http://en.wikipedia.org/wiki/HOXB13http://en.wikipedia.org/wiki/HOXB13http://www.genenames.org/data/hgnc_data.php?match=HOXC@http://en.wikipedia.org/wiki/Chromosome_12http://en.wikipedia.org/wiki/HOXC4http://en.wikipedia.org/wiki/HOXC5http://en.wikipedia.org/wiki/HOXC5http://en.wikipedia.org/wiki/HOXC6http://en.wikipedia.org/wiki/HOXC6http://en.wikipedia.org/wiki/HOXC8http://en.wikipedia.org/wiki/HOXC8http://en.wikipedia.org/wiki/HOXC9http://en.wikipedia.org/wiki/HOXC9http://en.wikipedia.org/wiki/HOXC10http://en.wikipedia.org/wiki/HOXC11http://en.wikipedia.org/wiki/HOXC11http://en.wikipedia.org/wiki/HOXC12http://en.wikipedia.org/wiki/HOXC12http://en.wikipedia.org/wiki/HOXC13http://www.genenames.org/data/hgnc_data.php?match=HOXD@http://en.wikipedia.org/wiki/Chromosome_2http://en.wikipedia.org/wiki/HOXD1http://en.wikipedia.org/wiki/HOXD3http://en.wikipedia.org/wiki/HOXD3http://en.wikipedia.org/wiki/HOXD4http://en.wikipedia.org/wiki/HOXD4http://en.wikipedia.org/wiki/HOXD8http://en.wikipedia.org/wiki/HOXD8http://en.wikipedia.org/wiki/HOXD9http://en.wikipedia.org/wiki/HOXD9http://en.wikipedia.org/wiki/HOXD10http://en.wikipedia.org/wiki/HOXD11http://en.wikipedia.org/wiki/HOXD12http://en.wikipedia.org/wiki/HOXD12http://en.wikipedia.org/wiki/HOXD13http://en.wikipedia.org/wiki/Genehttp://en.wikipedia.org/wiki/Genehttp://en.wikipedia.org/wiki/Transcription_factorshttp://en.wikipedia.org/wiki/Transcription_factorshttp://en.wikipedia.org/wiki/Octapeptidehttp://en.wikipedia.org/wiki/Octapeptidehttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/PAX1http://en.wikipedia.org/wiki/Amino_acidhttp://en.wikipedia.org/wiki/Exonhttp://en.wikipedia.org/wiki/PAX2http://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Renal-coloboma_syndromehttp://en.wikipedia.org/wiki/Renal-coloboma_syndromehttp://en.wikipedia.org/w/index.php?title=Oligomeganephronia&action=edit&redlink=1http://en.wikipedia.org/wiki/Pax_genes#cite_note-1http://en.wikipedia.org/wiki/Chromosomehttp://www.genenames.org/data/hgnc_data.php?match=HOXA@http://en.wikipedia.org/wiki/Chromosome_7_(human)http://en.wikipedia.org/wiki/Homeobox_A1http://en.wikipedia.org/wiki/HOXA2http://en.wikipedia.org/wiki/HOXA3http://en.wikipedia.org/wiki/HOXA4http://en.wikipedia.org/wiki/HOXA5http://en.wikipedia.org/wiki/HOXA6http://en.wikipedia.org/wiki/HOXA7http://en.wikipedia.org/wiki/HOXA9http://en.wikipedia.org/wiki/HOXA10http://en.wikipedia.org/wiki/HOXA11http://en.wikipedia.org/wiki/HOXA13http://www.genenames.org/data/hgnc_data.php?match=HOXB@http://en.wikipedia.org/wiki/Chromosome_17http://en.wikipedia.org/wiki/HOXB1http://en.wikipedia.org/wiki/HOXB2http://en.wikipedia.org/wiki/HOXB3http://en.wikipedia.org/wiki/HOXB4http://en.wikipedia.org/wiki/HOXB5http://en.wikipedia.org/wiki/HOXB6http://en.wikipedia.org/wiki/HOXB7http://en.wikipedia.org/wiki/HOXB8http://en.wikipedia.org/wiki/HOXB9http://en.wikipedia.org/wiki/HOXB13http://www.genenames.org/data/hgnc_data.php?match=HOXC@http://en.wikipedia.org/wiki/Chromosome_12http://en.wikipedia.org/wiki/HOXC4http://en.wikipedia.org/wiki/HOXC5http://en.wikipedia.org/wiki/HOXC6http://en.wikipedia.org/wiki/HOXC8http://en.wikipedia.org/wiki/HOXC9http://en.wikipedia.org/wiki/HOXC10http://en.wikipedia.org/wiki/HOXC11http://en.wikipedia.org/wiki/HOXC12http://en.wikipedia.org/wiki/HOXC13http://www.genenames.org/data/hgnc_data.php?match=HOXD@http://en.wikipedia.org/wiki/Chromosome_2http://en.wikipedia.org/wiki/HOXD1http://en.wikipedia.org/wiki/HOXD3http://en.wikipedia.org/wiki/HOXD4http://en.wikipedia.org/wiki/HOXD8http://en.wikipedia.org/wiki/HOXD9http://en.wikipedia.org/wiki/HOXD10http://en.wikipedia.org/wiki/HOXD11http://en.wikipedia.org/wiki/HOXD12http://en.wikipedia.org/wiki/HOXD13http://en.wikipedia.org/wiki/Genehttp://en.wikipedia.org/wiki/Transcription_factorshttp://en.wikipedia.org/wiki/Transcription_factorshttp://en.wikipedia.org/wiki/Octapeptidehttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/PAX1http://en.wikipedia.org/wiki/Amino_acidhttp://en.wikipedia.org/wiki/Exonhttp://en.wikipedia.org/wiki/PAX2http://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Renal-coloboma_syndromehttp://en.wikipedia.org/wiki/Renal-coloboma_syndromehttp://en.wikipedia.org/w/index.php?title=Oligomeganephronia&action=edit&redlink=1http://en.wikipedia.org/wiki/Pax_genes#cite_note-1 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9A1)has been identified with ear, eye and facial development. :t
transcribes a /25 amino acid protein in humans. (utations in it can
cause ;aardenburg syndrome. 9A1)is fre
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E- La )amilia del gen Dl23Distalless4:a* miem)ros
Operan en pares $os c#a$es est&n estrec'amente asocia"os con $os genes o-
D$-8 * D$- est&n $oca$i/a"os en posicin 8 .8 prima en re$acin a o-a14
D$-4 * D$-K son 85 a o-)14
D$-1 * D$-2 son 85a o-"14
La !ami$ia "e genes Dl2: contiene miem)ros * "esempean !#ncionesimportantes en $os procesos "e esta)$ecimiento "e$ patrn corpora$ .en especia$
$os es)o/os "e $os miem)ros% Los genes D$- "e $os mam!eros act6an en pareas
* m#estran #na asociacin estrec'a con $os o-% 7am)i?n inter>ienen en $a
!ormacin "e ma-i$ares * o"o interno
7ra)aan en e$ "esarro$$o "e $os ap?n"ices * en $a mor!og?nesis "e $a man")#$a
* "e$ o"o interno%
F- Los genes Ms2 3muscle segment $omeoo24Dos miem)ros, Ms-1 * Ms-2
Son in'i)i"ores "e $a "i!erenciacin en etapa prenata$, mientras #e en etapa pos
nata$ mantienen $a capaci"a" "e pro$i!eracin "e $os tei"os%
Importantes en $as re$aciones epite$iomesen#imatosas en $as e-tremi"a"es * $a
cara%
8- Los genes #-o2: .7)-7ienen #na regin conser>a"a, $a caa 7, #e co"i!ica "e 1G0 a 200 amino&ci"os,
#e se #ne en !orma espec!ica a$ ADN
a* m&s "e 100 miem)ros%
7ienen #e >er con $a in"#ccin "e$ meso"ermo, * si $a e-tremi"a" en "esarro$$o
es #n )ra/o o #na pierna
T-boxrefers to a group of transcription factorsinvolvedin limband heartdevelopment
>enes encoding T-box proteins include$
T7'!*TBR1
T71!*TBX1
T71"*TBX2
T71)*TBX3
T71/*TBX4
T713*TBX5
T714*TBX6
T71!6*TBX10
T71!3*TBX15
T71!8*TBX18
T71!5*TBX19
T71"6*TBX20
T71"!*TBX21
T71""*TBX22
/- Los )actores de transcripcin $lice 9 lao 9 $lice
http://en.wikipedia.org/wiki/Transcription_factorhttp://en.wikipedia.org/wiki/Limb_developmenthttp://en.wikipedia.org/wiki/Limb_developmenthttp://en.wikipedia.org/wiki/Hearthttp://en.wikipedia.org/wiki/TBR1http://en.wikipedia.org/wiki/TBR1http://www.genenames.org/data/hgnc_data.php?match=TBR1http://en.wikipedia.org/wiki/TBX1http://www.genenames.org/data/hgnc_data.php?match=TBX1http://en.wikipedia.org/wiki/TBX2http://www.genenames.org/data/hgnc_data.php?match=TBX2http://en.wikipedia.org/wiki/TBX3http://www.genenames.org/data/hgnc_data.php?match=TBX3http://en.wikipedia.org/w/index.php?title=TBX4&action=edit&redlink=1http://www.genenames.org/data/hgnc_data.php?match=TBX4http://en.wikipedia.org/wiki/TBX5_(gene)http://www.genenames.org/data/hgnc_data.php?match=TBX5http://en.wikipedia.org/w/index.php?title=TBX6&action=edit&redlink=1http://www.genenames.org/data/hgnc_data.php?match=TBX6http://en.wikipedia.org/w/index.php?title=TBX10&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=TBX10&action=edit&redlink=1http://www.genenames.org/data/hgnc_data.php?match=TBX10http://en.wikipedia.org/w/index.php?title=TBX15&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=TBX15&action=edit&redlink=1http://www.genenames.org/data/hgnc_data.php?match=TBX15http://en.wikipedia.org/w/index.php?title=TBX18&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=TBX18&action=edit&redlink=1http://www.genenames.org/data/hgnc_data.php?match=TBX18http://en.wikipedia.org/wiki/TBX19http://www.genenames.org/data/hgnc_data.php?match=TBX19http://en.wikipedia.org/wiki/TBX20http://www.genenames.org/data/hgnc_data.php?match=TBX20http://en.wikipedia.org/wiki/TBX21http://www.genenames.org/data/hgnc_data.php?match=TBX21http://en.wikipedia.org/wiki/TBX22http://www.genenames.org/data/hgnc_data.php?match=TBX22http://en.wikipedia.org/wiki/Transcription_factorhttp://en.wikipedia.org/wiki/Limb_developmenthttp://en.wikipedia.org/wiki/Hearthttp://en.wikipedia.org/wiki/TBR1http://www.genenames.org/data/hgnc_data.php?match=TBR1http://en.wikipedia.org/wiki/TBX1http://www.genenames.org/data/hgnc_data.php?match=TBX1http://en.wikipedia.org/wiki/TBX2http://www.genenames.org/data/hgnc_data.php?match=TBX2http://en.wikipedia.org/wiki/TBX3http://www.genenames.org/data/hgnc_data.php?match=TBX3http://en.wikipedia.org/w/index.php?title=TBX4&action=edit&redlink=1http://www.genenames.org/data/hgnc_data.php?match=TBX4http://en.wikipedia.org/wiki/TBX5_(gene)http://www.genenames.org/data/hgnc_data.php?match=TBX5http://en.wikipedia.org/w/index.php?title=TBX6&action=edit&redlink=1http://www.genenames.org/data/hgnc_data.php?match=TBX6http://en.wikipedia.org/w/index.php?title=TBX10&action=edit&redlink=1http://www.genenames.org/data/hgnc_data.php?match=TBX10http://en.wikipedia.org/w/index.php?title=TBX15&action=edit&redlink=1http://www.genenames.org/data/hgnc_data.php?match=TBX15http://en.wikipedia.org/w/index.php?title=TBX18&action=edit&redlink=1http://www.genenames.org/data/hgnc_data.php?match=TBX18http://en.wikipedia.org/wiki/TBX19http://www.genenames.org/data/hgnc_data.php?match=TBX19http://en.wikipedia.org/wiki/TBX20http://www.genenames.org/data/hgnc_data.php?match=TBX20http://en.wikipedia.org/wiki/TBX21http://www.genenames.org/data/hgnc_data.php?match=TBX21http://en.wikipedia.org/wiki/TBX22http://www.genenames.org/data/hgnc_data.php?match=TBX22 -
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A 3rotenas )&sicas '?$ice $a/o '?$ice
3rotenas #e contienen #n corto tramo "e amino&ci"os en $a c#a$ "os '?$ices
a$!a son separa"as por #n $a/o .$oop "e amino&ci"os% Esta regin, con #na
regin )&sica a"*acente, permite a esta protena reg#$a"ora #nirse a sec#encias
espec!icas "e ADN%
Las regiones )&sicas "e estas protenas se #nen a$ ADN,E$ "ominio '?$ice$a/o'?$ice est& in>o$#cra"o en 'omo"imeri/acin o
'etero"imeri/aicin%
Com6n en genes #e reg#$an $a miog?nesis%
B T>*palindromic, however some b+@+ transcription factors, notably those of theb+@+-9ABfamily, bind to related non-palindromic se
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3rotenas #e tienen #)ica"os en !orma reg#$ar #ni"a"es "e cisti"ina e 'isti"ina,
#e est&n #ni"os a iones "e /inc #e ca#sa #e $a ca"ena "e po$ip?pti"os se
"o)$e en estr#ct#ras como "e"os%
Estos "e"os se #nen a $#gares espec!icos a$ ADN
Inc$#*e a $as sig#ientes !ami$ias:
A Los genes So-
Genes 'o2 prote7nas 'o2Constit#*en #na gran !ami$ia .m&s "e 20 miem)ros, s#s componentes tienen en
com6n #n "ominio MF .gr#pos "e mo>i$i"a" a$ta en $a protena% Este
"ominio, #nto a #na protena compaera .asocia"a, se #ne a siete n#c$eti"os
en e$ s#rco menor * no en e$ s#rco ma*or "e $a '?$ice "e ADN * pro>oca #n
cam)io importante en s# con!ormacin%
Una caracterstica "e $os genes So- es #e tra)aan en con#nto con otros
!actores "e transcripcin, para $ograr $a e-presin "e $os genes%
El gen '!; es de este grupo0
Se e-presan en to"as $as estr#ct#ras en "i!erentes etapas "e$ "esarro$$o%
Otros !actores "e transcripcin:
Box genes are classified into groups. Box genes from different groups share little similarity
outside the DNA-binding domain. :n mouse and human the members of the groups are$ /#
BoxA$SRY
Box7!$ SOX1, SOX2,SOX3 Box7"$ SOX14,SOX21
Box$ SOX4, SOX11,SOX12
BoxD$ SOX5, SOX6,SOX13
Box$SOX8, SOX9,SOX10
BoxE$ SOX7, SOX17,SOX18
Box>$SOX15
Box+$ SOX30
II- M&LE%5LA' DE 'EN:Estas sa$en "e $as c?$#$as #e $as pro"#cen * eercen s#s e!ectos so)re otras c?$#$as, #e
p#e"en estar cerca o a gran "istancia% Se 'a "esc#)ierto #e $a misma mo$?c#$a "e
sea$i/acin p#e"e ser #sa"a en "i!erentes $#gares * en "i!erentes etapas "e$ "esarro$$o
"e$ em)rin%
Los !actores #e contro$an $oca$mente, ta$es como $a "#racin o $a concentracin "e $a
mo$?c#$a "e sea$i/acin, "eterminan e$ "estino "e$ gr#po "e c?$#$as respon"e"oras%
Estas mo$?c#$as sea$i/a"oras se #nen a mo$?c#$as receptoras, #e s#e$en ser protenas
transmem)rana #e protr#*en a tra>?s "e $a mem)rana p$asm&tica "e $as c?$#$as% Con $a
http://en.wikipedia.org/wiki/SOX_gene_family#cite_note-4http://en.wikipedia.org/wiki/SRYhttp://en.wikipedia.org/wiki/SRYhttp://en.wikipedia.org/wiki/SOX1http://en.wikipedia.org/wiki/SOX2http://en.wikipedia.org/wiki/SOX3http://en.wikipedia.org/wiki/SOX3http://en.wikipedia.org/wiki/SOX14http://en.wikipedia.org/wiki/SOX14http://en.wikipedia.org/wiki/SOX21http://en.wikipedia.org/wiki/SOX4http://en.wikipedia.org/wiki/SOX11http://en.wikipedia.org/wiki/SOX12http://en.wikipedia.org/wiki/SOX12http://en.wikipedia.org/wiki/SOX5http://en.wikipedia.org/wiki/SOX6http://en.wikipedia.org/wiki/SOX13http://en.wikipedia.org/wiki/SOX13http://en.wikipedia.org/wiki/SOX8http://en.wikipedia.org/wiki/SOX8http://en.wikipedia.org/wiki/SOX9http://en.wikipedia.org/wiki/SOX9http://en.wikipedia.org/wiki/SOX10http://en.wikipedia.org/w/index.php?title=SOX7&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=SOX17&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=SOX17&action=edit&redlink=1http://en.wikipedia.org/wiki/SOX18http://en.wikipedia.org/wiki/SOX15http://en.wikipedia.org/wiki/SOX15http://en.wikipedia.org/w/index.php?title=SOX30&action=edit&redlink=1http://en.wikipedia.org/wiki/SOX_gene_family#cite_note-4http://en.wikipedia.org/wiki/SRYhttp://en.wikipedia.org/wiki/SOX1http://en.wikipedia.org/wiki/SOX2http://en.wikipedia.org/wiki/SOX3http://en.wikipedia.org/wiki/SOX14http://en.wikipedia.org/wiki/SOX21http://en.wikipedia.org/wiki/SOX4http://en.wikipedia.org/wiki/SOX11http://en.wikipedia.org/wiki/SOX12http://en.wikipedia.org/wiki/SOX5http://en.wikipedia.org/wiki/SOX6http://en.wikipedia.org/wiki/SOX13http://en.wikipedia.org/wiki/SOX8http://en.wikipedia.org/wiki/SOX9http://en.wikipedia.org/wiki/SOX10http://en.wikipedia.org/w/index.php?title=SOX7&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=SOX17&action=edit&redlink=1http://en.wikipedia.org/wiki/SOX18http://en.wikipedia.org/wiki/SOX15http://en.wikipedia.org/w/index.php?title=SOX30&action=edit&redlink=1 -
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#nin oc#rre #na casca"a "e !enmenos en #na >a "e trans"#ccin "e sea$, #e 'ace
#e $a sea$ $$eg#e 'asta e$ n6c$eo%
A signaling moleculeis a moleculeinvolved in transmitting informationbetween cellsof a living multicellularorganism, or between organisms of the
same or different species.
:n a multicellular organism, signaling between cells occurs either throughrelease into the extracellular space, divided in paracrinesignaling *over shortdistances and endocrinesignaling *over long distances, or by direct contact,&nown asjuxtacrine signaling.!#Autocrinesignaling is a special case ofparacrine signaling where the secreting cell has the ability to respond to thesecreted signaling molecule."# Bynapticsignaling is a special case of paracrinesignaling *for chemical synapses or juxtacrine signaling *forelectricalsynapses between neuronsand target cells. Bignaling molecules interact witha target cell as a ligandto cell surface receptors, andCor by entering into the cell
through its membraneor endocytosisfor intracrinesignaling. This generallyresults in the activation of second messengers,leading to various physiologicaleffects.
+ormonesare the major signaling molecules of the endocrine system,
though they often regulate each otherFs secretion via local signaling
*e.g.islet of @angerhanscells, and most are also expressed in tissues for
local purposes *e.g. angiotensin or failing that,structurally relatedmolecules
are *e.g. 9T+r9.
Neurotransmittersare signaling molecules of the nervous system, also
including neuropeptidesand neuromodulators. Neurotransmitters li&e
the catecholaminesare also secreted by the endocrine system into the
systemic circulation.
yto&inesare signaling molecules of the immune system, with a primary
paracrine or juxtacrine role, though they can during significant immune
responses have a strong presence in the circulation, with systemic effect
*altering iron metabolismor body temperature. >rowth factorscan be
considered as cyto&ines or a different class.
?-
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Como eemp$o est& 7Fos "e 40 amino&ci"os% E$
prec#rsor g$icosi$a"o est& constit#i"o por #na pe#ea sec#encia Ntermina$
sea$i/a"ora, #na proregin m#c'o ma*or * #na regin C termina$ "e 112
amino&ci"os )ioacti>a% La proregin es escin"i"a 12arngea12amente "e $a regin
)ioacti>a por #na /ona "e c#atro amino&ci"os )&sicos #)ica"a #nto a$ "ominio)ioacti>o% 7ras s# secrecin por $a c?$#$a, $a proregin "e $a mo$?c#$a permanece
asocia"a a $a regin )ioacti>a, 'acien"o #e $a mo$?c#$a se mantenga en esta"o
$atente% El d7mero ioacti.o slo adquiere su acti.idad iolgica tras ladisociacin entre la proregin la regin ioacti.a0
Una "e $as s#)!ami$ias m&s importantes "e $a !ami$ia "e #GF-@, es $a !ami$ia "e $asprotenas mor!ogen?ticas seas% L$e>an este nom)re por#e inicia$mente se
"esc#)rieron como $os agentes in"#ctores "e$ proceso "e c#racin "e #na !ract#ra%
Son 18 miem)ros% #egan #n pape$ importante en e$ "esarro$$o "e $a ma*or parte "e
$as estr#ct#ras "e$ em)rin%
Us#a$mente eercen s# e!ecto in'i)ien"o otros procesos en e$ em)rin%3ara 'acer m&s comp$ica"o esto a$g#nos procesos "e$ "esarro$$o oc#rren por $a
in'i)icin "e BM3s, como en e$ caso "e$ "esarro$$o "e$ sistema ner>ioso centra$%
Las mo$?c#$as #e in'i)en o antagoni/an $a accin "e $as BM3s son: estas
mo$?c#$as se #nen a $os "meros "e BM3s secreta"os, e inter!ieren con s# #nin a
receptores espec!icos%
Miem)ro entric#$ares
Acti>ina 3ro$i!eracin "e c?$#$as "e $a gran#$osa
In"#ccin meso"?rmica
In'i)ina In'i)icin "e $a secrecin "e gona"otropinas por $a
'ip!isis
S#stancia "e in'i)icin
m#$$eriana
Regresin "e $os con"#ctos parameson?!ricos
Decapentap$?ico Sea$i/acin para e$ "esarro$$o "e $os miem)ros
Pg1 In"#ccin "e$ meso"ermo * $a $nea primiti>aDe BM31 a BM3 In"#ccin "e $a p$aca ne#ra$, "i!erenciacin es#e$?tica *
otras in"#cciones
No"a$ a"o "e $a $nea "e
c?$#$as g$ia$es
In"#ccin "e$ crecimiento "e$ es)o/o #retera$,
co$oni/acin ne#ra$ "e$ intestino
Le!t* Determinacin "e $a asimetra corpora$
T>E-G is a secreted proteinthat exists in at least three isoformscalled T>E-
G!, T>E- G "and T>E- G ). :t was also the original name for T>E-G!, which wasthe founding member of this family. The T>E-G family is part of a superfamily of
http://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Protein_isoformhttp://en.wikipedia.org/wiki/TGF_beta_1http://en.wikipedia.org/wiki/TGF_beta_1http://en.wikipedia.org/wiki/TGF_beta_1http://en.wikipedia.org/wiki/TGF_beta_2http://en.wikipedia.org/wiki/TGF_beta_2http://en.wikipedia.org/wiki/TGF_beta_3http://en.wikipedia.org/wiki/TGF_beta_3http://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Protein_isoformhttp://en.wikipedia.org/wiki/TGF_beta_1http://en.wikipedia.org/wiki/TGF_beta_1http://en.wikipedia.org/wiki/TGF_beta_2http://en.wikipedia.org/wiki/TGF_beta_3 -
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proteins &nown as the transforming growth factor beta superfamily, whichincludes inhibins,activin, anti-mHllerian hormone, bone morphogeneticprotein, decapentaplegicand Ig-!.
T>E-G pertenece a una superfamilia de factores de crecimientoE-G *!,",) y otros factores variados,como 7(9, activinas,inhibinasy la hormona antimHlleriana.!@a molJcula conuna funciKn mLs amplia es T>E-G! y es la ar s#s
receptores%
Estim#$an entre otros e$ crecimiento "e $os capi$ares
S# reg#$acin:
a mo"i!icacin "e s# interaccin con 'eparan proteog$icanos en e$ comp$eo con e$
receptor
) reg#$acin a ni>e$ "e $a mem)rana "e $a c?$#$a respon"e"ora a tra>?s "e $a accin
"e protenas transmem)rana
c reg#$acin interce$#$ar por mo$?c#$as ta$es como spro#t*, $a c#a$ 'ace comp$eos
con partes "e $a ma#inaria "e $a >a "e trans"#ccin "e $a c?$#$a respon"e"ora%
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Creta ecto"?rmica apica$ en e$ crecimiento "e $os miem)ros
Es)o/o "e$ esma$te en $os "ientes en "esarro$$o
Estim#$a $a pro$i!eracin "e$ mesen#ima "e $os ma-i$ares
esc#$as
pticas * "e$ te$enc?!a$o
In"#ccin temprana "e $os "ientes
Estim#$a $a pro$i!eracin "e$ meso"ermo "e $a cresta ne#ra$ en $a
regin !rontonasa$
Estim#$a $a pro$i!eracin "e$ mesen#ima "e $os ma-i$ares
In"#ccin "e $as papi$as !i$i!ormes "e $a $eng#a
In"#ccin 'ep&tica temprana
Crecimiento "e$ t#)?rc#$o genita$
E!throughE>E!6all bind fibroblast growth factor
receptors*E>E's. E>E!is also &nown as ac!"!c, andE>E"is also &nown as #as!c
$!#r%#last &r%'t( $act%r.
(embersE>E!!,E>E!", E>E!),andE>E!/,also &nown as E>E homologous factors
!-/ *E+E!-E+E/, have been shown to have distinct $u)ct!%)aldifferences compared to the
E>Es. Although these factors possess remar&ably similar seE'sand are involved in intracellular processes unrelated to the E>Es. /#This group
is also &nown as =iE>E=.3#
+uman E>E!8is involved in cell development and morphogenesis in various tissues
including cartilage.4#
+uman E>E"6was identified based on its homology toX*)%+usE>E-"6 *1E>E-"6.2#8#
E>E!3through E>E")were described later and functions are still being
characteri%ed. E>E!3is the mouse ortholog of humanE>E!5*there is no human E>E!3
and, where their functions are shared, they are often described as E>E!3C!5.5#:n contrast
to the local activity of the other E>Es, E>E!3C!5, E>E"!andE>E")have systemic effects.5#!6#
http://en.wikipedia.org/wiki/Signaling_moleculehttp://en.wikipedia.org/wiki/Signaling_moleculehttp://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-1http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-2http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-3http://en.wikipedia.org/wiki/FGF1http://en.wikipedia.org/wiki/FGF1http://en.wikipedia.org/wiki/FGF10http://en.wikipedia.org/wiki/FGF10http://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptorhttp://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptorhttp://en.wikipedia.org/wiki/FGF1http://en.wikipedia.org/wiki/FGF2http://en.wikipedia.org/wiki/FGF2http://en.wikipedia.org/wiki/FGF11http://en.wikipedia.org/wiki/FGF11http://en.wikipedia.org/wiki/FGF12http://en.wikipedia.org/wiki/FGF12http://en.wikipedia.org/wiki/FGF13http://en.wikipedia.org/wiki/FGF13http://en.wikipedia.org/wiki/FGF14http://en.wikipedia.org/wiki/FGF14http://en.wikipedia.org/wiki/FGF14http://en.wikipedia.org/wiki/FGFRhttp://en.wikipedia.org/wiki/FGFRhttp://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-4http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-5http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-5http://en.wikipedia.org/wiki/FGF18http://en.wikipedia.org/wiki/FGF18http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-pmid15896984-6http://en.wikipedia.org/wiki/FGF20http://en.wikipedia.org/wiki/FGF20http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-pmid10441498-7http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-pmid10441498-7http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-8http://en.wikipedia.org/wiki/FGF15http://en.wikipedia.org/wiki/FGF15http://en.wikipedia.org/wiki/FGF23http://en.wikipedia.org/wiki/FGF15http://en.wikipedia.org/wiki/FGF19http://en.wikipedia.org/wiki/FGF19http://en.wikipedia.org/wiki/FGF15/19http://en.wikipedia.org/wiki/FGF15/19http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-pmid22302876-9http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-pmid22302876-9http://en.wikipedia.org/wiki/FGF21http://en.wikipedia.org/wiki/FGF21http://en.wikipedia.org/wiki/FGF23http://en.wikipedia.org/wiki/FGF23http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-pmid22302876-9http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-10http://en.wikipedia.org/wiki/Signaling_moleculehttp://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-1http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-2http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-3http://en.wikipedia.org/wiki/FGF1http://en.wikipedia.org/wiki/FGF10http://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptorhttp://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptorhttp://en.wikipedia.org/wiki/FGF1http://en.wikipedia.org/wiki/FGF2http://en.wikipedia.org/wiki/FGF11http://en.wikipedia.org/wiki/FGF12http://en.wikipedia.org/wiki/FGF13http://en.wikipedia.org/wiki/FGF14http://en.wikipedia.org/wiki/FGFRhttp://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-4http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-5http://en.wikipedia.org/wiki/FGF18http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-pmid15896984-6http://en.wikipedia.org/wiki/FGF20http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-pmid10441498-7http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-8http://en.wikipedia.org/wiki/FGF15http://en.wikipedia.org/wiki/FGF23http://en.wikipedia.org/wiki/FGF15http://en.wikipedia.org/wiki/FGF19http://en.wikipedia.org/wiki/FGF15/19http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-pmid22302876-9http://en.wikipedia.org/wiki/FGF21http://en.wikipedia.org/wiki/FGF23http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-pmid22302876-9http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-10 -
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Receptors[edit source| edit beta]
The mammalian fibroblast growth factor receptorfamily has /
members, E>E'!, E>E'",E>E'), and E>E'/. The E>E's consist of three
extracellular immunoglobulin-type domains *D!-D), a single-span trans-
membrane domain and an intracellular split tyrosine &inasedomain. E>Esinteract with the D" and D) domains, with the D) interactions primarily
responsible for ligand-binding specificity *see below. +eparan sulfate binding is
mediated through the D) domain. A short stretch of acidic amino acids located
between the D! and D" domains has auto-inhibitory functions. This Facid boxF
motif interacts with the heparan sulfate binding site to prevent receptor
activation in the absence of E>Es.
Es in developmental processesinclude mesoderminduction, antero-posterior patterning,2#limb development,
neural induction and neural development,!4#
and in maturetissuesCsystemsangiogenesis, &eratinocyte organi%ation, and woundhealingprocesses.
0ne important function of E>E! and E>E" is the promotion ofendothelialcellproliferation and the physical organi%ation of endothelial cells into tube-li&estructures. They thus promoteangiogenesis, the growth of new bloodvesselsfrom the pre-existing vasculature. E>E! and E>E" are more potentangiogenic factors than vascular endothelial growth factor*I>E orplatelet-derived growth factor*9D>E.""#E>E! has been shown in clinical experimentalstudies to induce angiogenesis in the heart. "!#
/- Familia $edge$og4 miem)ros: sonic, in"ian, "esert
Uno "e s#s miem)ros Sonic 'e"ge'og, res#$ta !#n"amenta$
3rotena con #na porcin ntermina$ a$tamente conser>a"a * #na regin c
termina$ m&s >aria)$e%
L#ego "e $a sntesis * $i)eracin "e$ po$ip?pti"o por e$ retc#$o en"op$asmico, e$
p?pti"o "e sea$ es separa"o * oc#rre g$icosi$acin en e$ resto "e$ p?pti"o% A#n
"entro "e $a c?$#$a, e$ p?pti"o s'' s#!re a#torompimiento a tra>?s "e $a acti>i"a"
cata$tica "e s# porcin ctermina$% D#rante s# rompimiento, $a porcin n
termina$ se #ne a$ co$estero$% Esta mo$?c#$a "e 1 Da$tons, ntermina$, #ni"a a$co$estero$ es secreta"a "e $a c?$#$a% 7o"a $a acti>i"a" "e sea$i/acin "e s''
resi"e en esta porcin ntermina$%
En $a s#per!icie "e $a c?$#$a )$anco, se #ne a #n receptor $$ama"o patc$ed, esteest& estrec'amente re$aciona"o con #na mo$?c#$a transmem)rana, #na protena
$$ama"a smoot$ened% Norma$mente patc$edin'i)e $a acti>i"a" "e sea$i/acin"e smoot$ened% S'' a$ #nirse a patc'e" permite a smoot'ene" #e en>e #nasea$ a$ interior "e $a c?$#$a%
'$$in'i)e $a acti>i"a" in'i)itoria "e patc$ed0A tra>?s "e $a participacin "e otras mo$?c#$as en e$ citop$asma, $as c#a$es est&n
norma$mente #ni"as a microt6)#$os, !ina$mente smoot$enedacti>a e$ !actor "e
http://en.wikipedia.org/w/index.php?title=Fibroblast_growth_factor&action=edit§ion=2http://en.wikipedia.org/w/index.php?title=Fibroblast_growth_factor&veaction=edit§ion=2http://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptorhttp://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptorhttp://en.wikipedia.org/wiki/FGFR1http://en.wikipedia.org/wiki/FGFR2http://en.wikipedia.org/wiki/FGFR2http://en.wikipedia.org/wiki/FGFR3http://en.wikipedia.org/wiki/FGFR4http://en.wikipedia.org/wiki/Tyrosine_kinasehttp://en.wikipedia.org/wiki/Mesodermhttp://en.wikipedia.org/wiki/Mesodermhttp://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-pmid10441498-7http://en.wikipedia.org/wiki/Limb_developmenthttp://en.wikipedia.org/wiki/Limb_developmenthttp://en.wikipedia.org/wiki/Neural_developmenthttp://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-16http://en.wikipedia.org/wiki/Angiogenesishttp://en.wikipedia.org/wiki/Wound_healinghttp://en.wikipedia.org/wiki/Wound_healinghttp://en.wikipedia.org/wiki/Endothelial_cellhttp://en.wikipedia.org/wiki/Endothelial_cellhttp://en.wikipedia.org/wiki/Endothelial_cellhttp://en.wikipedia.org/wiki/Angiogenesishttp://en.wikipedia.org/wiki/Angiogenesishttp://en.wikipedia.org/wiki/Blood_vesselhttp://en.wikipedia.org/wiki/Blood_vesselhttp://en.wikipedia.org/wiki/Vascular_endothelial_growth_factorhttp://en.wikipedia.org/wiki/Platelet-derived_growth_factorhttp://en.wikipedia.org/wiki/Platelet-derived_growth_factorhttp://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-22http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-stegman-21http://en.wikipedia.org/w/index.php?title=Fibroblast_growth_factor&action=edit§ion=2http://en.wikipedia.org/w/index.php?title=Fibroblast_growth_factor&veaction=edit§ion=2http://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptorhttp://en.wikipedia.org/wiki/FGFR1http://en.wikipedia.org/wiki/FGFR2http://en.wikipedia.org/wiki/FGFR3http://en.wikipedia.org/wiki/FGFR4http://en.wikipedia.org/wiki/Tyrosine_kinasehttp://en.wikipedia.org/wiki/Mesodermhttp://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-pmid10441498-7http://en.wikipedia.org/wiki/Limb_developmenthttp://en.wikipedia.org/wiki/Neural_developmenthttp://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-16http://en.wikipedia.org/wiki/Angiogenesishttp://en.wikipedia.org/wiki/Wound_healinghttp://en.wikipedia.org/wiki/Wound_healinghttp://en.wikipedia.org/wiki/Endothelial_cellhttp://en.wikipedia.org/wiki/Endothelial_cellhttp://en.wikipedia.org/wiki/Angiogenesishttp://en.wikipedia.org/wiki/Blood_vesselhttp://en.wikipedia.org/wiki/Blood_vesselhttp://en.wikipedia.org/wiki/Vascular_endothelial_growth_factorhttp://en.wikipedia.org/wiki/Platelet-derived_growth_factorhttp://en.wikipedia.org/wiki/Platelet-derived_growth_factorhttp://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-22http://en.wikipedia.org/wiki/Fibroblast_growth_factor#cite_note-stegman-21 -
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transcripcin ;"e"o /inc 8= .8/inc !inger $$ama"o Gli, e$ c#a$ se m#e>e a$interior "e$ n6c$eo * se #ne a #n sitio espec!ico "e$ ADN%
The hedgehog gene *(( was first identified in the fruit-fly Dr%s%+(!la*la)%&ast*r.
0f the ((homologues, SHHhas been found to have the most critical roles indevelopment, acting as a morphogen involved in patterning many systems,including the limb3#and midline structures in the brain,!"#spinal cord,!)#the thalamusby the-%)a l!!ta)s !)trat(ala!ca !/#and the teeth.!3#(utationsin the human sonic hedgehog gene, SHH, cause holoprosencephalytype )+9) as a result of the loss of the ventralmidline
Patterning of the central nervous system[edit source| edit beta]
The sonic hedgehog *B++ signaling molecule assumes various roles in
patterning the central nervous system*NB during vertebrate development.0ne of the most characteri%ed functions of B++ is its role in the induction of
the floor plateand diverse ventral cell types within the neural tube."6#The notochord, a structure derived from the axial mesoderm, produces B++
which travels extracellularly to the ventral region of the neural tube and instructs
those cells to form the floor plate."!#Another view for floor plate induction
hypothesi%e that some precursor cells located in notochord are inserted into the
neural plate before its formation, later giving rise to floor plate. ""#
B++ exerts its effects in a concentration-dependent manner,"8#so that a high
concentration of B++ results in a local inhibitionof cellular proliferation.
"5#
Thisinhibition causes the floor plate to become thin compared to the lateral regionsof the neural tube. @ower concentration of B++ results in cellular proliferationand induction of various ventral neural cell types."4#0nce the floor plateisestablished, cells residing in this region will subse
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6- Familia Cnt1G miem)ros
#ega #n pape$ ma*or en e$ proceso "e $a gastr#$acin .tercera semana "e$
"esarro$$o
La !orma en #e act6a es comp$ea% Lo 'ace a tra>?s "e )etacatenina% En
a#sencia "e nt, en e$ interior "e $a c?$#$a, )eta catenina est& #ni"a a #ncomp$eo "e "estr#ccin * es "egra"a"a% C#an"o se presenta nt, se #ne a #n
receptor en $a s#per!icie "e $a c?$#$a $$ama"o iene $a "egra"acin "e )eta ca"enina%
Beta ca"enina entonces entra a$ n6c$eo en "on"e !orma comp$eos con otros
!actores "e transcripcin, para !ina$mente #nirse a$ ADN * acti>ar $a
transcripcin%
Reg#$acin: s# acti>i"a" p#e"e ser in'i)i"a por otras mo$?c#$as in'i)itorias% E$
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Proteins[edit source| edit beta]
rystal protein structure of ;nt8 and the cysteine-rich domain of Eri%%led 8.
The ;nt proteins are a diverse family of secreted lipid-modified
signaling glycoproteinsthat are )36/66 amino acidsin length.2#The type of
lipid modification that occurs on these proteins ispalmitoylationof cysteinesin a
conserved pattern of ")"/ cysteine residues.)#9almitoylation is necessary
because it initiates targeting of the ;nt protein to theplasma membranefor
secretion and it allows the ;nt protein to bind its receptor. ;nt proteins also
undergoglycosylation, which insures proper secretion.8#:n ;nt signaling, these
proteins act as ligandsto activate the different ;nt pathways via paracrine and
autocrine routes.!#/#
pecies !nt proteins
H%% sa+!*)s
;nt!,;nt",;nt"7,;nt),;nt)A,;nt/, ;nt3A,
;nt37, ;nt4,;nt2A,;nt27,;nt8A,;nt87, ;nt5A,
;nt57, ;nt!6A, ;nt!67,;nt!!, ;nt!4
"oundation[edit source| edit beta]
;nt signaling begins when one of the ;nt proteins binds the N-terminal extra-
cellular cysteine-rich domain of a Eri%%led*E% family receptor.!6#These
receptors span the plasma membraneseven times and constitute a distinct
family of >-protein coupled receptors*>9's.!!#+owever, to facilitate ;nt
signaling, co-receptorsmay also be re
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protein*@'9-3C4, receptor tyrosine &inase*'y&, and '0'"./#Ppon activation
of the receptor, a signal is sent to the phosphoproteinDishevelled*Dsh, which
is located in thecytoplasm. This signal is transmitted via a direct interaction
between E% and Dsh. Dsh proteins are present in all organisms and they all
share the following highly conserved protein domains$ an amino-
terminal D:1domain, a central 9DQdomain, and a carboxy-terminal D9domain. These different domains are important because after
Dsh, the ;nt signal can branch off into several different pathways and each
pathway interacts with a different combination of the three domains.!"#
Eigure !. ;nt doesnFt bind to the receptor. Axin, >B and A9 form a =destruction complex,= and G-at
is destroyed.
http://en.wikipedia.org/wiki/Lipoprotein_receptor-related_proteinhttp://en.wikipedia.org/wiki/Lipoprotein_receptor-related_proteinhttp://en.wikipedia.org/wiki/Receptor_tyrosine_kinasehttp://en.wikipedia.org/wiki/Receptor_tyrosine_kinasehttp://en.wikipedia.org/wiki/ROR2http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Komiya-4http://en.wikipedia.org/wiki/Phosphoproteinhttp://en.wikipedia.org/wiki/Dishevelledhttp://en.wikipedia.org/wiki/Cytoplasmhttp://en.wikipedia.org/wiki/Protein_domainshttp://en.wikipedia.org/w/index.php?title=DIX_domain&action=edit&redlink=1http://en.wikipedia.org/wiki/PDZ_domainhttp://en.wikipedia.org/wiki/DEP_domainhttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Dawid-12http://en.wikipedia.org/wiki/Lipoprotein_receptor-related_proteinhttp://en.wikipedia.org/wiki/Lipoprotein_receptor-related_proteinhttp://en.wikipedia.org/wiki/Receptor_tyrosine_kinasehttp://en.wikipedia.org/wiki/ROR2http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Komiya-4http://en.wikipedia.org/wiki/Phosphoproteinhttp://en.wikipedia.org/wiki/Dishevelledhttp://en.wikipedia.org/wiki/Cytoplasmhttp://en.wikipedia.org/wiki/Protein_domainshttp://en.wikipedia.org/w/index.php?title=DIX_domain&action=edit&redlink=1http://en.wikipedia.org/wiki/PDZ_domainhttp://en.wikipedia.org/wiki/DEP_domainhttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Dawid-12 -
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Eigure ". ;nt binds to *activates the receptor. Axin is removed from the =destruction complex.= G-at
moves into the nucleus, binds to a transcription factor on DNA, and activates transcription of a protein.
=9= represents phosphate.
#anonical and noncanonical path$ays[edit source| edit beta]
The three best characteri%ed ;nt signaling pathways are the canonical ;nt
pathway, the noncanonical planar cell polarity pathway, and the noncanonical
;ntCcalcium pathway. As their names suggest, these pathways belong to one of
two categories$ canonical or noncanonical. The difference between the
categories is that a canonical pathway involves the protein G -cateninwhile a
noncanonical pathway operates independently of it. !6
http://en.wikipedia.org/wiki/Phosphatehttp://en.wikipedia.org/wiki/Phosphatehttp://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&action=edit§ion=5http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&veaction=edit§ion=5http://en.wikipedia.org/wiki/%CE%92-cateninhttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Rao-10http://en.wikipedia.org/wiki/Phosphatehttp://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&action=edit§ion=5http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&veaction=edit§ion=5http://en.wikipedia.org/wiki/%CE%92-cateninhttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Rao-10 -
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The canonical !nt path$ay[edit source| edit beta]The canonical !nt path$ay*or ;ntCG-catenin pathway is the ;nt pathway
that causes an accumulation of G-catenin in the cytoplasm and its eventual
translocation into the nucleusto act as a
transcriptional coactivatorof transcription factorsthat belong to the TEC@E
family. ;ithout ;nt signaling, the G-catenin would not accumulate in the
cytoplasm since a destruction complex would normally degrade it. This
destruction complex includes the following proteins$Axin, adenomatosis
polyposis coli*A9, protein phosphatase "A*99"A, glycogen synthase
&inase )*>B) and casein &inase ! ?*!?. :t degrades G-catenin by
targeting it for ubi
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The noncanonical planar cell polarity path$ay[edit source| edit beta]
The noncanonical planar cell polarity (P#P) path$ayis one of the two ;nt
pathways that does not involve G-catenin. :t does not use @'9-3C4 as its co-
receptor and is thought to use N'+!, 'y&, 9T2, or '0'". As in the canonical
;nt pathway, the 99 pathway is activated via the binding of ;nt to E% and its
co-receptor. The receptor then recruits Dsh, which uses its 9DQ and D9
domains to form a complex with Dishevelled-associated activator of
morphogenesis ! *DAA(!. Daam! then activates the small >-
protein'hothrough a guanine exchange factor. 'ho activates 'ho-associated
&inase *'0, which is one of the major regulators of thecytos&eleton. Dsh
also forms a complex with rac!and mediatesprofilinbinding to actin. 'ac!
activates RNand can also lead to actin polymeri%ation. 9rofilin binding to actin
can result in restructuring of the cytos&eleton and gastrulation./#!/#
The noncanonical !nt%calcium path$ay[edit source|edit beta]
The noncanonical !nt%calcium path$ayis the other ;nt pathway that does
not stimulate accumulation of G-catenin. :ts role is to help regulate calciumrelease from the endoplasmic reticulum *' in order to control intracellular
http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&action=edit§ion=7http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&veaction=edit§ion=7http://en.wikipedia.org/wiki/PTK7http://en.wikipedia.org/wiki/DAAM1http://en.wikipedia.org/wiki/G-proteinhttp://en.wikipedia.org/wiki/G-proteinhttp://en.wikipedia.org/wiki/Rho_family_of_GTPaseshttp://en.wikipedia.org/wiki/Cytoskeletonhttp://en.wikipedia.org/wiki/Cytoskeletonhttp://en.wikipedia.org/wiki/Rac1http://en.wikipedia.org/wiki/Profilinhttp://en.wikipedia.org/wiki/Profilinhttp://en.wikipedia.org/wiki/Actinhttp://en.wikipedia.org/wiki/JNKhttp://en.wikipedia.org/wiki/Gastrulationhttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Komiya-4http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-pmid16793760-14http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&action=edit§ion=8http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&veaction=edit§ion=8http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&veaction=edit§ion=8http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&action=edit§ion=7http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&veaction=edit§ion=7http://en.wikipedia.org/wiki/PTK7http://en.wikipedia.org/wiki/DAAM1http://en.wikipedia.org/wiki/G-proteinhttp://en.wikipedia.org/wiki/G-proteinhttp://en.wikipedia.org/wiki/Rho_family_of_GTPaseshttp://en.wikipedia.org/wiki/Cytoskeletonhttp://en.wikipedia.org/wiki/Rac1http://en.wikipedia.org/wiki/Profilinhttp://en.wikipedia.org/wiki/Actinhttp://en.wikipedia.org/wiki/JNKhttp://en.wikipedia.org/wiki/Gastrulationhttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Komiya-4http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-pmid16793760-14http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&action=edit§ion=8http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&veaction=edit§ion=8 -
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calcium levels. @i&e other ;nt pathways, upon ligand binding, the activated E%
receptor directly interacts with Dsh and activates specific Dsh-protein domains.
The domains involved in ;ntCcalcium signaling are the 9DQ and D9 domains./#+owever, unli&e other ;nt pathways, the E% receptor also directly interfaces
with a trimeric >-protein. This co-stimulation of Dsh and the >-protein can lead
to the activation of either 9@or c>(9-specific 9D.:f 9@ is activated, theplasma membrane component 9:9" is cleaved into DA> and :9). ;hen :9)
binds its receptor on the ', calcium is released. :ncreased concentrations of
calcium and DA> can activate dc/"through 9. dc/" is an important
regulator of cell adhesion, migration, and tissue separation. :ncreased calcium
also activates calcineurinand a(::. alcineurin induces activation of the
transcription factor NEAT, which regulates ventral patterning./#am:: activates
TA! and N@&inase, which can interfere with TECS-atenin signaling in the
canonical ;nt pathway.!3#+owever, if 9D is activated, calcium release from
the ' is inhibited. 9D mediates this through the inhibition of 9>, which
subse
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the posterior region and the areas of their lowest concentration indicate the
anterior region. :n fish and frogs, G-catenin produced by canonical ;nt signaling
causes the formation of organi%ing centers, which, alongside 7(9s, elicits
posterior formation. ;nt involvement in dorsoventral axis formation can be seen
in the activity of the formation of the Bpemann organi%er, which establishes the
dorsal region. anonical ;nt signaling production G-catenin induces theformation of this organi%er via the activation of the genes t'!)and s!a%!s.!8#!5#
;nt signaling is also involved in the axis formation of specific body parts and
organ systems that are a part of later development. :n vertebrates, sonic
hedgehog*Bhh and ;nt morphogenetic signaling gradients establish the
dorsoventral axis of the central nervous systemduring neural tubeaxial
patterning. +igh ;nt signaling establishes the dorsal region while high Bhh
signaling indicates in the ventral region. "6#;nt is also involved in the dorsal-
ventral formation of the central nervous system through its involvement in axon
guidance. ;nt proteins guide the axons of thespinal cordin an anterior-
posterior direction."!#;nt is also involved in the formation of the limb dorsal-ventral axis. Bpecifically, ;nt2a helps produce the dorsal patterning of the
developing limb.!8#!5#
#ell fate specification[edit source| edit beta]
ell fate specification, or cell differentiation, is a cellular process where
undifferentiated cells can become a more speciali%ed cell type. ;nt signaling
induces differentiation of pluripotent stem
cellsinto mesodermand endodermprogenitor cells.""#These progenitor cells
are then further induced to differentiate into more specific cell types such asendothelial, cardiac, and vascular smooth muscle lineages.")#;nt signaling can
also induce blood formation from stem cells. Bpecifically, ;nt) leads to
mesoderm committed cells with hematopoieticpotential."/#;nt! has also been
shown to antagoni%e neural differentiation and is a major factor in self-renewal
of neural stem cells. This allows for regeneration of nervous system cells, which
is further evidence of a role in promoting neural stem cell proliferation. ""#;nt
signaling has also been shown to be involved in germ
celldetermination, guttissue specification, hair follicledevelopment, lung tissue
development, trun& neural crest celldifferentiation, nephrondevelopment, ovary
development, and sex determination.!8#
#ell proliferation[edit source| edit beta]
:n order to have the mass differentiation of cells needed to form the specified
cell tissues of different organisms, a proliferation, or cell growth, of embryonic
stem cells must ta&e place. This process is mediated through canonical ;nt
signaling, which increases nuclear and cytoplasmic level of G-catenin. :ncreased
levels of G-catenin can initiate transcriptional activation of proteins such
as cyclin D!and cc, which control the>!to B phasetransition in the cell
cycle. ntry into the B phase causes DNA replicationand ultimately mitosis,which are responsible for cell proliferation. "3#This increase in proliferation is
http://en.wikipedia.org/wiki/Spemann_organizerhttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Gilbert-18http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-pmid19736321-19http://en.wikipedia.org/wiki/Shhhttp://en.wikipedia.org/wiki/Shhhttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Neural_tubehttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-20http://en.wikipedia.org/wiki/Axon_guidancehttp://en.wikipedia.org/wiki/Axon_guidancehttp://en.wikipedia.org/wiki/Spinal_cordhttp://en.wikipedia.org/wiki/Spinal_cordhttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-21http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Gilbert-18http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-pmid19736321-19http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&action=edit§ion=14http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&veaction=edit§ion=14http://en.wikipedia.org/wiki/Pluripotent_stem_cellshttp://en.wikipedia.org/wiki/Pluripotent_stem_cellshttp://en.wikipedia.org/wiki/Mesodermhttp://en.wikipedia.org/wiki/Endodermhttp://en.wikipedia.org/wiki/Progenitor_cellshttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Nusse08-22http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-23http://en.wikipedia.org/wiki/Hematopoietichttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-24http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Nusse08-22http://en.wikipedia.org/wiki/Germ_cellhttp://en.wikipedia.org/wiki/Germ_cellhttp://en.wikipedia.org/wiki/Gut_(anatomy)http://en.wikipedia.org/wiki/Hair_folliclehttp://en.wikipedia.org/wiki/Neural_crest_cellhttp://en.wikipedia.org/wiki/Nephronhttp://en.wikipedia.org/wiki/Sex-determination_systemhttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Gilbert-18http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&action=edit§ion=15http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&veaction=edit§ion=15http://en.wikipedia.org/wiki/Cyclin_D1http://en.wikipedia.org/wiki/C-mychttp://en.wikipedia.org/wiki/G1_phasehttp://en.wikipedia.org/wiki/G1_phasehttp://en.wikipedia.org/wiki/S_phasehttp://en.wikipedia.org/wiki/Cell_cyclehttp://en.wikipedia.org/wiki/Cell_cyclehttp://en.wikipedia.org/wiki/DNA_replicationhttp://en.wikipedia.org/wiki/Mitosishttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-25http://en.wikipedia.org/wiki/Spemann_organizerhttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Gilbert-18http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-pmid19736321-19http://en.wikipedia.org/wiki/Shhhttp://en.wikipedia.org/wiki/Shhhttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Neural_tubehttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-20http://en.wikipedia.org/wiki/Axon_guidancehttp://en.wikipedia.org/wiki/Axon_guidancehttp://en.wikipedia.org/wiki/Spinal_cordhttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-21http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Gilbert-18http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-pmid19736321-19http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&action=edit§ion=14http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&veaction=edit§ion=14http://en.wikipedia.org/wiki/Pluripotent_stem_cellshttp://en.wikipedia.org/wiki/Pluripotent_stem_cellshttp://en.wikipedia.org/wiki/Mesodermhttp://en.wikipedia.org/wiki/Endodermhttp://en.wikipedia.org/wiki/Progenitor_cellshttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Nusse08-22http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-23http://en.wikipedia.org/wiki/Hematopoietichttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-24http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Nusse08-22http://en.wikipedia.org/wiki/Germ_cellhttp://en.wikipedia.org/wiki/Germ_cellhttp://en.wikipedia.org/wiki/Gut_(anatomy)http://en.wikipedia.org/wiki/Hair_folliclehttp://en.wikipedia.org/wiki/Neural_crest_cellhttp://en.wikipedia.org/wiki/Nephronhttp://en.wikipedia.org/wiki/Sex-determination_systemhttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-Gilbert-18http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&action=edit§ion=15http://en.wikipedia.org/w/index.php?title=Wnt_signaling_pathway&veaction=edit§ion=15http://en.wikipedia.org/wiki/Cyclin_D1http://en.wikipedia.org/wiki/C-mychttp://en.wikipedia.org/wiki/G1_phasehttp://en.wikipedia.org/wiki/S_phasehttp://en.wikipedia.org/wiki/Cell_cyclehttp://en.wikipedia.org/wiki/Cell_cyclehttp://en.wikipedia.org/wiki/DNA_replicationhttp://en.wikipedia.org/wiki/Mitosishttp://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-25 -
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directly paired with cell differentiation because as the stem cells proliferate, they
are differentiated into the specific tissues that are induced to become. This
allows for overall growth and development of specific tissue systems during
embryonic development. This is apparent in systems such as the circulatory
system where ;nt)a leads to proliferation and expansion of hematopoietic
stem cells needed for red blood cell formation."4#
#ell migration
ell migration during embryonic development allows for the establishment of
body axes, tissue formation, limb induction, and several other processes. ;nt
signaling helps mediate this process, particularly during convergent extension.
'esearch has shown that signaling from both the ;nt 99 pathway and
canonical ;nt pathway is ree/ son mo$?c#$as
in'i)itorias%
http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-26http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-27http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-28http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-26http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-27http://en.wikipedia.org/wiki/Wnt_signaling_pathway#cite_note-28 -
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I"- #!AN'D5%%I>N DE LA 'Ear
$a sea$ a$ n6c$eo "e $a c?$#$a, en "on"e in!$#*e en $a e-presin "e #n gen%
Es com6n 'a)$ar "e estas >as "e trans"#ccin "e sea$ como $inea$es, pero en
rea$i"a" $as >as "e trans"#ccin "e sea$ son #na >er"a"era re", s#etas a #na
gran >arie"a" "e estm#$os mo"#$a"ores% a* >arias >as "e trans"#ccin "e
sea$%
Los miem)ros "e $a !ami$ia "e$ !actor "e crecimiento "e $os !i)ro)$astos .an"o #n a"o, act6a >a protenas F .protenas #e se #nen ag#anosinatri!os!ato * a g#anosina"i!os!ato, #e estim#$a $a en/ima e!ectora
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.eemp$o a"eni$ato cic$asa para con>ertir $as mo$?c#$as prec#rsoras en seg#n"os
mensaeros% Dos seg#n"os mensaeros signi!icati>os son e$ a"enosin
mono!os!ato cc$ico * e$ inosntri!os!ato m&s "iaci$g$icero$% A contin#acin, e$
seg#n"o mensaero acti>a $as proteincinasas citop$asm&ticas #e in"#cen $a
!os!ori$acin .aa"en gr#pos !os!ato en $as protenas "iana, acti>&n"o$as o
inacti>&n"o$as% 3#e"e 'a)er otros pasos pero "esp#?s "e esto oc#rre e$ paso "e $amo$?c#$a acti>a"a a$ n6c$eo, * se pro"#ce #n e!ecto so)re $a transcripcin "e$
DNA%
"- A%ID& !E#IN&I%&Meta)o$ito "e $a >itamina A% Pitamina #e $$ega a$ em)rin como retino$%
E$ retino$ se acop$a a #na protena "e #nin * a s# >e/ se a"'iere a receptores
espec!icos en $a s#per!icie "e $a c?$#$a% Entra en e$ citop$asma * es $i)era"o "e
este comp$eo "on"e se #ne a #na prote7na de unin al retinol celular3%!1(?40En e$ citop$asma, e$ retino$ to"o trans es con>erti"o2arngea2amente primero a retina$ to"o trans * $#ego en &ci"o retinoicoto"o trans, #e es e$ retinoi"e con acti>i"a" )io$gica m&s potente% a* "os
protenas, CRB3 * CRAB3 3prote7na de unin al cido retinoico celular4#ereg#$an $a canti"a" "e retinoi"es #e a$can/an e$ n6c$eo% Una >e/ $i)era"o a
partir "e CRAB3, entra en e$ n6c$eo, "on"e se #ne a #n 'etero"mero constit#i"o
por #n miem)ro "e $a !ami$ia "e$ receptor del cido retinoico 3!A!4 al)a etao gama* Retinoi" @ receptor "e $a !ami$ia a$!a, )eta o gama% Este comp$eo!orma"o por &ci"o retinoico m&s e$ 'etero"imero a$ ;e$emento "e$ resp#esta "e$
&ci"o retinoico= en e$ ADN% .P?ase $a !ig#ra * act6a como #n !actor "e
transcripcin contro$an"o e$ pro"#cto "e #n gen%
E$ &ci"o retinoico es pro"#ci"o * #ti$i/a"o en regiones $oca$es espec!icas
"#rante $a etapa prenata$ * $a posnata$%
Una "e s#s !#nciones conoci"as en $as !ases inicia$es "e$ "esarro$$o son a$g#nos
genes o- .o-)1 por eemp$o, canti"a"es ins#!icientes o e-cesi>as "e &ci"o
retinoico p#e"e "ar $#gar a trastornos gra>es en $a organi/acin "e$
rom)enc?!a$o * "e $a cresta ne#ra$ 2arngea%
"I- M&LE%5LA' DE AD+E'I>N7res son $as m&s importantes
1 Ca"erinas2 IgCAMs
4 NCAMs
4 Integrinas
Los $igan"os "e $a matri/ e-trace$#$ar interact6an con receptores "e $as
c?$#$as >ecinas%
Matri/ e-trace$#$ar: !orma"a por mo$?c#$as como co$&geno, proteog$#canos
.s#$!ato "e con"roitina, &ci"o 'ia$#rnico, etc * g$#coprotenas como
!i)ronectina * $aminina%
Los receptores #e #nen a $as mo$?c#$as e-trace$#$ares, como !i)ronectina *
$aminina se $$aman integrinas0
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Estos receptores integran a $as m$ec#$as "e $a matri/ e-trace$#$ar en #na
ma#inaria citoes#e$?tica se !orma #n sistema "e migracin para $as
c?$#$as meso"?rmicas%
GENE' 5E IN#E!"IENEN EN EL DE'A!!&LL& ; %AN%E!
A$g#nos "e $os genes #e participan en e$ "esarro$$o em)rionario #na >e/ #e m#tan"an $#gar a "i>ersos c&nceres% a* "os gr#pos "e genes imp$ica"os en esto:
1 Los protooncogenes: p#e"en con>ertirse en oncogenes #e son $os ca#santes
rea$es "e $a pro$i!eracin ce$#$ar "escontro$a"a% Los protooncogenes "irigen $a
!ormacin norma$ "e mo$?c#$as tan "i>ersas como ciertos !actores "e
crecimiento, receptores "e !actores "e crecimiento, protenas "e sea$i/acin "e
mem)rana * citop$asm&ticas * !actores "e transcripcin%
In"#cen $a !ormacin t#mora$ a tra>?s "e mecanismos "e ganancia "e !#ncin%
2 Los genes s#presores t#mora$es: #e s#e$en act#ar $imitan"o $a !rec#encia "e $as
"i>isiones ce$#$ares% Los a$e$os recesi>os, con per"i"a "e $a !#ncin "e estos
genes no p#e"en s#primir $a "i>isin ce$#$ar, $o #e 'ace #e apare/can"i>isiones incontro$a"as en po)$aciones ce$#$ares "e!ini"as%
4