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Diabetes Publish Ahead of Print published online ahead of print January 17, 2007
DOI: 10.2337/db06-1187
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Original Research

Novel function of the ciliogenic transcription factor RFX3 in development of the endocrine pancreas

Aouatef Ait-Lounis1, Dominique Baas2,,3, Emmanuèle Barras1, Carine Benadiba2, Anne Charollais4, Rachel Nlend Nlend4, Delphine Liègeois4, Paolo Meda4, Bénédicte Durand2, and Walter Reith1

1Department of Pathology and Immunology, University of Geneva Medical School, 1 Rue Michel-Servet, CH-1211, Geneva, Switzerland
2Centre de Génétique Moléculaire et Cellulaire, Université Claude Bernard Lyon-1, 43 Boulevard du 11 Novembre 1918, F-69622, Villeurbanne, France
3Present Address, Equipe Différenciation Neuromusculaire, 46 allée d'Italie, F-69364, Lyon, France
4Department of Cell Physiology and Metabolism, University of Geneva Medical School, 1 Rue Michel-Servet, CH-1211, Geneva, Switzerland

Correspondence: walter.reith{at}medecine.unige.ch

The transcription factor RFX3 regulates the expression of genes required for the growth and function of cilia. We show here that mouse RFX3 is expressed specifically in developing and mature pancreatic endocrine cells during embryogenesis and in adults. RFX3 expression is already 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 are consequently 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 peptide 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.


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Copyright © 2007 by the American Diabetes Association.