Author
Listed:
- Stuart B. Smith
(Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA)
- Hui-Qi Qu
(McGill University, Montreal, Québec H3H 1P3, Canada)
- Nadine Taleb
(McGill University, Montreal, Québec H3H 1P3, Canada)
- Nina Y. Kishimoto
(Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA)
- David W. Scheel
(Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA)
- Yang Lu
(McGill University, Montreal, Québec H3H 1P3, Canada)
- Ann-Marie Patch
(Institute of Biomedical and Clinical Science, Peninsula Medical School)
- Rosemary Grabs
(McGill University, Montreal, Québec H3H 1P3, Canada)
- Juehu Wang
(Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA)
- Francis C. Lynn
(Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA
Present address: Departments of Surgery and Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, British Columbia V5Z 4H4, Canada.)
- Takeshi Miyatsuka
(Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA)
- John Mitchell
(McGill University, Montreal, Québec H3H 1P3, Canada)
- Rina Seerke
(Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA)
- Julie Désir
(Hôpital Erasme-ULB)
- Serge Vanden Eijnden
(Hôpital Erasme-ULB)
- Marc Abramowicz
(Hôpital Erasme-ULB)
- Nadine Kacet
(Hôpital Calmette)
- Jacques Weill
(Hôpital Calmette)
- Marie-Ève Renard
(Hôpital Calmette)
- Mattia Gentile
(Medical Genetic Unit, Di Venere General Hospital)
- Inger Hansen
(Emory University School of Medicine, Atlanta, Georgia 30322, USA)
- Ken Dewar
(McGill University, and Research Institute of the McGill University Health Centre, Montreal, Quebec H3A 1B1, Canada)
- Andrew T. Hattersley
(Institute of Biomedical and Clinical Science, Peninsula Medical School)
- Rennian Wang
(Pharmacology & Medicine, Child Health Research Institute, the University of Western Ontario, London, Ontario N6C 2V5, Canada)
- Maria E. Wilson
(Metabolex Inc., Hayward, California 94545, USA)
- Jeffrey D. Johnson
(Metabolex Inc., Hayward, California 94545, USA)
- Constantin Polychronakos
(McGill University, Montreal, Québec H3H 1P3, Canada)
- Michael S. German
(Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA
University of California San Francisco, San Francisco, California 94143, USA)
Abstract
Insulin from the β-cells of the pancreatic islets of Langerhans controls energy homeostasis in vertebrates, and its deficiency causes diabetes mellitus. During embryonic development, the transcription factor neurogenin 3 (Neurog3) initiates the differentiation of the β-cells and other islet cell types from pancreatic endoderm, but the genetic program that subsequently completes this differentiation remains incompletely understood. Here we show that the transcription factor Rfx6 directs islet cell differentiation downstream of Neurog3. Mice lacking Rfx6 failed to generate any of the normal islet cell types except for pancreatic-polypeptide-producing cells. In human infants with a similar autosomal recessive syndrome of neonatal diabetes, genetic mapping and subsequent sequencing identified mutations in the human RFX6 gene. These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and humans. Rfx6 could prove useful in efforts to generate β-cells for patients with diabetes.
Suggested Citation
Stuart B. Smith & Hui-Qi Qu & Nadine Taleb & Nina Y. Kishimoto & David W. Scheel & Yang Lu & Ann-Marie Patch & Rosemary Grabs & Juehu Wang & Francis C. Lynn & Takeshi Miyatsuka & John Mitchell & Rina , 2010.
"Rfx6 directs islet formation and insulin production in mice and humans,"
Nature, Nature, vol. 463(7282), pages 775-780, February.
Handle:
RePEc:nat:nature:v:463:y:2010:i:7282:d:10.1038_nature08748
DOI: 10.1038/nature08748
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