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Role of the Onecut transcription factors in pancreas morphogenesis and in pancreatic and enteric endocrine differentiation

Authors: Marjorie Jenny; Vinciane Vanhorenbeeck; Guy G. Rousseau; Frédéric P. Lemaigre; Patrick Jacquemin; Jean-François Cornut; Gérard Gradwohl;

Role of the Onecut transcription factors in pancreas morphogenesis and in pancreatic and enteric endocrine differentiation

Abstract

The Onecut (OC) transcription factor HNF-6 (OC-1) is required during embryogenesis for pancreatic specification, morphogenesis and endocrine differentiation. In mammals, HNF-6 has two paralogs, OC-2 and OC-3, which share DNA-binding and transcriptional activation properties and have expression patterns that overlap with that of HNF-6. This suggested that OC-2 and OC-3 play redundant roles with HNF-6 in pancreas development. Here, we have addressed this hypothesis by analyzing the phenotype of mice knockout for the Onecut factors. We found that neither OC-2 nor OC-3 is required for pancreas specification. However, OC-2 plays partially redundant roles with HNF-6 in pancreas morphogenesis and in the differentiation of endocrine precursors. As similar molecular events drive endocrine differentiation in the pancreas and gastrointestinal tract, we also investigated if Onecut factors are involved in enteroendocrine differentiation. OC-2 and OC-3 were found to delineate specific antero-posterior regions of the gut around embryonic day 12.5. Later on, OC2 was expressed in several gut cell types, whereas OC-3 behaved as a specific marker of the enteroendocrine lineage. However, OC-2 and OC-3, alone or in combination, were dispensable for gut development and enteroendocrine differentiation. In conclusion, our data reveal partially redundant roles for HNF-6 and OC-2 in developing pancreas and identify new markers for antero-posterior patterning of the gut and for enteroendocrine differentiation.

Keywords

Male, Enteroendocrine Cells, Cell Line, Ngn3, Mice, Insulin-Secreting Cells, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Animals, Gut, Molecular Biology, Pancreas, Body Patterning, Homeodomain Proteins, Mice, Knockout, Onecut, Endocrine differentiation, Gene Expression Regulation, Developmental, Cell Differentiation, Cell Biology, Rats, Hepatocyte Nuclear Factor 6, Female, Developmental Biology, Onecut Transcription Factors, Transcription Factors

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
57
Top 10%
Top 10%
Top 10%
hybrid