title: Novel function of the ciliogenic transcription factor RFX3 in development of the endocrine pancreas.
abstract: The transcription factor regulatory factor X (RFX)-3 regulates the expression of genes required for the growth and function of cilia. We show here that mouse RFX3 is expressed in developing and mature pancreatic endocrine cells during embryogenesis and in adults. RFX3 expression already is evident in early Ngn3-positive progenitors and is maintained in all major pancreatic endocrine cell lineages throughout their development. Primary cilia of hitherto unknown function present on these cells consequently are reduced in number and severely stunted in Rfx3(-/-) mice. This ciliary abnormality is associated with a developmental defect leading to a uniquely altered cellular composition of the islets of Langerhans. Just before birth, Rfx3(-/-) islets contain considerably less insulin-, glucagon-, and ghrelin-producing cells, whereas pancreatic polypeptide-positive cells are markedly increased in number. In adult mice, the defect leads to small and disorganized islets, reduced insulin production, and impaired glucose tolerance. These findings suggest that RFX3 participates in the mechanisms that govern pancreatic endocrine cell differentiation and that the presence of primary cilia on islet cells may play a key role in this process.
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, 1 Rue Michel-Servet, CH-1211, Geneva, Switzerland.
authors.forename: Aouatef
authors.initials: A
authors.lastname: Ait-Lounis
authors.forename: Dominique
authors.initials: D
authors.lastname: Baas
authors.forename: Emmanuèle
authors.initials: E
authors.lastname: Barras
authors.forename: Carine
authors.initials: C
authors.lastname: Benadiba
authors.forename: Anne
authors.initials: A
authors.lastname: Charollais
authors.forename: Rachel
authors.initials: R
authors.lastname: Nlend Nlend
authors.forename: Delphine
authors.initials: D
authors.lastname: Liègeois
authors.forename: Paolo
authors.initials: P
authors.lastname: Meda
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Durand
authors.forename: Walter
authors.initials: W
authors.lastname: Reith
mesh_terms: D000818:Animals; D002923:Cilia / Q000502:physiology / Q000648:ultrastructure; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005260:Female; D054439:Ghrelin; D005951:Glucose Tolerance Test; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D036361:Peptide Hormones / Q000032:analysis; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D035181:TATA-Box Binding Protein / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D054439:Ghrelin; D036361:Peptide Hormones; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; C000605541:Rfx3 protein, mouse; D035181:TATA-Box Binding Protein; D014157:Transcription Factors