Reference : Rfx6 is an Ngn3-dependent winged helix transcription factor required for pancreatic i...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/73291
Rfx6 is an Ngn3-dependent winged helix transcription factor required for pancreatic islet cell development.
English
Soyer, Josselin [University of Strasbourg > Inserm U-964, CNRS UMR7104 > Institute of Genetics and Molecular and Cell Biology (IGBMC) > >]
Flasse, Lydie [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
Raffelsberger, Wolfgang [University of Strasbourg > Inserm U-964, CNRS UMR7104 > Institute of Genetics and Molecular and Cell Biology (IGBMC) > >]
Beucher, Anthony [University of Strasbourg > Inserm U-964, CNRS UMR7104 > Institute of Genetics and Molecular and Cell Biology (IGBMC) > >]
Orvain, Christophe [University of Strasbourg > Inserm U-964, CNRS UMR7104 > Institute of Genetics and Molecular and Cell Biology (IGBMC) > >]
Peers, Bernard mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
Ravassard, Philippe [Université Pierre et Marie Curie > CNRS UMR7225, Inserm UMRS795 > Centre de Recherche de l’Institut du Cerveau et de la Moelle > >]
Vermot, Julien [University of Strasbourg > Inserm U-964, CNRS UMR7104 > Institute of Genetics and Molecular and Cell Biology (IGBMC) > >]
Voz, Marianne mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
Mellitzer, Georg [University of Strasbourg > Inserm U-964, CNRS UMR7104 > Institute of Genetics and Molecular and Cell Biology (IGBMC) > >]
Gradwohl, Gerard [University of Strasbourg > Inserm U-964, CNRS UMR7104 > Institute of Genetics and Molecular and Cell Biology (IGBMC) > >]
Jan-2010
Development
Company of Biologists
137
2
203-12
Yes (verified by ORBi)
International
0950-1991
1477-9129
Cambridge
United Kingdom
[en] Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; Blotting, Northern ; Cells, Cultured ; Embryo, Mammalian/metabolism ; Embryo, Nonmammalian/metabolism ; Endocrine Cells/cytology/metabolism ; Endoderm/metabolism ; Gene Expression Regulation, Developmental ; Ghrelin/metabolism ; Glucagon/metabolism ; Homeodomain Proteins/genetics/metabolism ; Immunohistochemistry ; In Situ Hybridization ; Islets of Langerhans/cytology/metabolism ; Mice ; Nerve Tissue Proteins/genetics/metabolism ; Paired Box Transcription Factors/genetics/metabolism ; Pancreas/cytology/embryology/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Somatostatin/metabolism ; Stem Cells/cytology/metabolism ; Transcription Factors/genetics/metabolism ; Winged-Helix Transcription Factors/genetics/metabolism ; Zebrafish ; Zebrafish Proteins/genetics/metabolism
[en] The transcription factor neurogenin 3 (Neurog3 or Ngn3) controls islet cell fate specification in multipotent pancreatic progenitor cells in the mouse embryo. However, our knowledge of the genetic programs implemented by Ngn3, which control generic and islet subtype-specific properties, is still fragmentary. Gene expression profiling in isolated Ngn3-positive progenitor cells resulted in the identification of the uncharacterized winged helix transcription factor Rfx6. Rfx6 is initially expressed broadly in the gut endoderm, notably in Pdx1-positive cells in the developing pancreatic buds, and then becomes progressively restricted to the endocrine lineage, suggesting a dual function in both endoderm development and islet cell differentiation. Rfx6 is found in postmitotic islet progenitor cells in the embryo and is maintained in all developing and adult islet cell types. Rfx6 is dependent on Ngn3 and acts upstream of or in parallel with NeuroD, Pax4 and Arx transcription factors during islet cell differentiation. In zebrafish, the Rfx6 ortholog is similarly found in progenitors and hormone expressing cells of the islet lineage. Loss-of-function studies in zebrafish revealed that rfx6 is required for the differentiation of glucagon-, ghrelin- and somatostatin-expressing cells, which, in the absence of rfx6, are blocked at the progenitor stage. By contrast, beta cells, whose number is only slightly reduced, were no longer clustered in a compact islet. These data unveil Rfx6 as a novel regulator of islet cell development.
Giga-Development and Stem Cells
http://hdl.handle.net/2268/73291
10.1242/dev.041673
http://dev.biologists.org/content/137/2/203.long

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