PUBLICATION

Organ-specific requirements for Hdac1 in liver and pancreas formation

Authors
Noël, E.S., Casal-Sueiro, A., Busch-Nentwich, E., Verkade, H., Dong, P.D., Stemple, D.L., and Ober, E.A.
ID
ZDB-PUB-080825-31
Date
2008
Source
Developmental Biology   322(2): 237-250 (Journal)
Registered Authors
Busch-Nentwich, Elisabeth, Dong, P. Duc, Noël, Emily, Ober, Elke, Stemple, Derek L., Verkade, Heather
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Cell Differentiation/physiology
  • Cell Proliferation
  • Endoderm/embryology
  • Hepatocytes/cytology
  • Hepatocytes/physiology
  • Histone Deacetylase 1
  • Histone Deacetylases/genetics
  • Histone Deacetylases/metabolism*
  • Liver/embryology*
  • Liver/enzymology
  • Lung/embryology
  • Lung/enzymology
  • Molecular Sequence Data
  • Mutation
  • Organ Specificity
  • Pancreas/embryology*
  • Pancreas/enzymology
  • Zebrafish/embryology*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
18687323 Full text @ Dev. Biol.
Abstract
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes