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1.
Dev Biol ; 322(2): 237-50, 2008 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-18687323

RESUMEN

Liver, pancreas and lung originate from the presumptive foregut in temporal and spatial proximity. This requires precisely orchestrated transcriptional activation and repression of organ-specific gene expression within the same cell. Here, we show distinct roles for the chromatin remodelling factor and transcriptional repressor Histone deacetylase 1 (Hdac1) in endodermal organogenesis in zebrafish. Loss of Hdac1 causes defects in timely liver specification and in subsequent differentiation. Mosaic analyses reveal a cell-autonomous requirement for hdac1 within the hepatic endoderm. Our studies further reveal specific functions for Hdac1 in pancreas development. Loss of hdac1 causes the formation of ectopic endocrine clusters anteriorly to the main islet, as well as defects in exocrine pancreas specification and differentiation. In addition, we observe defects in extrahepatopancreatic duct formation and morphogenesis. Finally, loss of hdac1 results in an expansion of the foregut endoderm in the domain from which the liver and pancreas originate. Our genetic studies demonstrate that Hdac1 is crucial for regulating distinct steps in endodermal organogenesis. This suggests a model in which Hdac1 may directly or indirectly restrict foregut fates while promoting hepatic and exocrine pancreatic specification and differentiation, as well as pancreatic endocrine islet morphogenesis. These findings establish zebrafish as a tractable system to investigate chromatin remodelling factor functions in controlling gene expression programmes in vertebrate endodermal organogenesis.


Asunto(s)
Histona Desacetilasas/metabolismo , Hígado/embriología , Páncreas/embriología , Proteínas de Pez Cebra/metabolismo , Pez Cebra/embriología , Secuencia de Aminoácidos , Animales , Diferenciación Celular/fisiología , Proliferación Celular , Endodermo/embriología , Hepatocitos/citología , Hepatocitos/fisiología , Histona Desacetilasa 1 , Histona Desacetilasas/genética , Hígado/enzimología , Pulmón/embriología , Pulmón/enzimología , Datos de Secuencia Molecular , Mutación , Especificidad de Órganos , Páncreas/enzimología , Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética
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