Novel Function of the Ciliogenic Transcription Factor RFX3 in Development of the Endocrine Pancreas
Novel Function of the Ciliogenic Transcription Factor RFX3 in Development of the Endocrine Pancreas Aouatef Ait-Lounis 1 , Dominique Baas 2 3 , Emmanuèle Barras 1 , Carine Benadiba 2 , Anne Charollais 4 , Rachel Nlend Nlend 4 , Delphine Liègeois 4 , Paolo Meda 4 , Bénédicte Durand 2 and Walter Reith...
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Published in | Diabetes (New York, N.Y.) Vol. 56; no. 4; pp. 950 - 959 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.04.2007
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Subjects | |
Online Access | Get full text |
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Summary: | Novel Function of the Ciliogenic Transcription Factor RFX3 in Development of the Endocrine Pancreas
Aouatef Ait-Lounis 1 ,
Dominique Baas 2 3 ,
Emmanuèle Barras 1 ,
Carine Benadiba 2 ,
Anne Charollais 4 ,
Rachel Nlend Nlend 4 ,
Delphine Liègeois 4 ,
Paolo Meda 4 ,
Bénédicte Durand 2 and
Walter Reith 1
1 Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland
2 Centre de Génétique Moléculaire et Cellulaire, Université Claude Bernard, Villeurbanne, France
3 Equipe Différenciation Neuromusculaire, Lyon, France
4 Department of Cell Physiology and Metabolism, University of Geneva Medical School, Geneva, Switzerland
Address correspondence and reprint requests to Walter Reith, Department of Pathology and Immunology, University of Geneva
Medical School, 1 Rue Michel-Servet, CH-1211, Geneva, Switzerland. E-mail: walter.reith{at}medecine.unige.ch
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.
dpc, day postcoitum
Hh, hedgehog
IFT, intraflagellar transport
PP, pancreatic polypeptide
RFX, regulatory factor X
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 17 January 2007. DOI: 10.2337/db06-1187.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db06-1187 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted January 5, 2007.
Received August 25, 2006.
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0012-1797 1939-327X |
DOI: | 10.2337/db06-1187 |