Two HGEN Faculty Members published in nature

11-Feb-10

DewarPolychronakos

A recent article by  Ken Dewar and Constatin Polychronakos (et al.) was published in this week’s issue of nature: International weekly journal of science.

Article

Nature 463, 775-780 (11 February 2010) | doi:10.1038/nature08748; Received 30 June 2009; Accepted 7 December 2009

 

Rfx6 directs islet formation and insulin production in mice and humans

Stuart B. Smith1, Hui-Qi Qu2,12, Nadine Taleb2,12, Nina Y. Kishimoto1, David W. Scheel1, Yang Lu2, Ann-Marie Patch3, Rosemary Grabs2, Juehu Wang1, Francis C. Lynn1,13, Takeshi Miyatsuka1, John Mitchell2, Rina Seerke1, Julie Désir4, Serge Vanden Eijnden4, Marc Abramowicz4, Nadine Kacet5, Jacques Weill5, Marie-Ève Renard5, Mattia Gentile6, Inger Hansen7, Ken Dewar8, Andrew T. Hattersley3, Rennian Wang9, Maria E. Wilson10, Jeffrey D. Johnson10, Constantin Polychronakos2 & Michael S. German1,11

  1. Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA
  2. Departments of Paediatrics and Human Genetics, McGill University, Montreal, Québec H3H 1P3, Canada
  3. Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter EX2 5DW, UK
  4. Department of Neonatology, Hôpital Erasme-ULB, Brussels 1070, Belgium
  5. Department of Neonatology, Hôpital Calmette, 59037 Lille cedex, France
  6. Medical Genetic Unit, Di Venere General Hospital, 70012 Bari, Italy
  7. Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
  8. Department of Human Genetics, McGill University, and Research Institute of the McGill University Health Centre, Montreal, Quebec H3A 1B1, Canada
  9. Departments of Physiology, Pharmacology & Medicine, Child Health Research Institute, the University of Western Ontario, London, Ontario N6C 2V5, Canada
  10. Metabolex Inc., Hayward, California 94545, USA
  11. Department of Medicine, University of California San Francisco, San Francisco, California 94143, USA
  12. These authors contributed equally to this work.
  13. Present address: Departments of Surgery and Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, British Columbia V5Z 4H4, Canada.

Correspondence to: Constantin Polychronakos2Michael S. German1,11 Correspondence and requests for materials should be addressed to C.P. (Email: constantin.polychronakos@mcgill.ca) or M.S.G. (Email: mgerman@diabetes.ucsf.edu).

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.

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