title: 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.
authors.affiliation: Hormone and Metabolic Research Unit, Université catholique de Louvain and Christian de Duve Institute of Cellular Pathology, 75 Avenue Hippocrate, B-1200 Brussels, Belgium.
authors.forename: Vinciane
authors.initials: V
authors.lastname: Vanhorenbeeck
authors.forename: Marjorie
authors.initials: M
authors.lastname: Jenny
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Cornut
authors.forename: Gérard
authors.initials: G
authors.lastname: Gradwohl
authors.forename: Frédéric P
authors.initials: FP
authors.lastname: Lemaigre
authors.forename: Guy G
authors.initials: GG
authors.lastname: Rousseau
authors.forename: Patrick
authors.initials: P
authors.lastname: Jacquemin
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D019858:Enteroendocrine Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051559:Hepatocyte Nuclear Factor 6 / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051558:Onecut Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010179:Pancreas / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics
chemical_list: D051559:Hepatocyte Nuclear Factor 6; D018398:Homeodomain Proteins; C487964:ONECUT2 protein, mouse; D051558:Onecut Transcription Factors; C496606:Onecut1 protein, mouse; C454106:Onecut3 protein, mouse; D014157:Transcription Factors