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This version published online on December 16, 2004
Endocrinology, doi:10.1210/en.2004-1576
A more recent version of this article appeared on March 1, 2005
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Submitted on December 6, 2004
Accepted on December 8, 2004

Transcriptional regulation in pancreatic development

Joel F. Habener M.D.*, Daniel M. Kemp Ph.D., and Melissa K. Thomas MD, Ph.D.

Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, Novartis Pharmaceuticals Corporation, Cambridge, MA

* To whom correspondence should be addressed. E-mail: jhabener{at}partners.org.

Considerable progress has been made in the understanding of the sequential activations of signal transduction pathways and the expressions of transcription factors during pancreas development. Much of this understanding has been obtained by analyses of the phenotypes of mice in which the expression of key genes has been disrupted (knockout mice). Knockouts of the genes for Pdx1, Hlxb9, Isl1, and Hex result in an arrest of pancreas development at a very early stage (e8-9). Disruption of genes encoding components of the Notch signaling pathway, e.g. Hes1 or Ngn3, abrogates development of the endocrine pancreas (Islets of Langerhans). Disruption of transcription factor genes expressed more downstream in the developmental cascade (Beta2/NeuroD, Pax4, NKx2.2, Nkx6.1) curtails the formation of insulin-producing {beta} cells. Further, an understanding of the importance of transcription factor genes during pancreas development has provided insights into the pathogenesis of diabetes in which the mass of insulin-producing {beta} cells is reduced.
Key words: pancreas development • transcription factors • diabetes mellitus • Pdx-1 • MODY




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