Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Organ-specific requirements for Hdac1 in liver and pancreas formation.

Developmental biology | Oct 15, 2008

http://www.ncbi.nlm.nih.gov/pubmed/18687323

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.

Pubmed ID: 18687323 RIS Download

Mesh terms: Amino Acid Sequence | Animals | Cell Differentiation | Cell Proliferation | Endoderm | Hepatocytes | Histone Deacetylase 1 | Histone Deacetylases | Liver | Lung | Molecular Sequence Data | Mutation | Organ Specificity | Pancreas | Zebrafish | Zebrafish Proteins

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: Medical Research Council, Id: MC_U117581329

ZFIN (Data, Gene Expression)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.