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Tumour suppressor menin is essential for development of the pancreatic endocrine cells

Sandra Fontanière1, Bertrand Duvillié, Raphaël Scharfmann

  • 1CNRS UMR2501, Laboratoire Génétique Moléculaire, Signalisation et Cancer, Université Claude Bernard Lyon, Lyon F-69008, France.

The Journal of Endocrinology
|September 6, 2008
PubMed

Insights

The menin protein, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is crucial for pancreatic endocrine cell development. Loss of menin leads to apoptosis and impaired differentiation of these vital cells.

Area of Science:

  • Developmental Biology
  • Endocrinology
  • Genetics

Background:

  • Mutations in the multiple endocrine neoplasia type 1 (MEN1) gene are linked to MEN1, affecting endocrine tissues.
  • The role of the MEN1 gene in embryonic endocrine cell development is largely unknown.

Purpose of the Study:

  • To investigate the role of the MEN1 gene and its protein product, menin, in the embryonic development of pancreatic endocrine cells.

Main Methods:

  • Utilized homozygous Men1 knockout mice and chimerism assays.
  • Employed pancreatic bud culture to mimic alpha- and beta-cell differentiation.
  • Assessed cell apoptosis and expression of neurogenin 3.

Main Results:

  • Homozygous Men1 knockout mice showed reduced glucagon-positive cells and increased apoptosis in early pancreatic buds.
  • Menin demonstrated an autonomous and specific effect on islet cell development.
  • Loss of menin impaired endocrine cell differentiation, altered pancreatic structure, and decreased neurogenin 3 expression.

Conclusions:

  • Menin is essential for the survival of early pancreatic endocrine cells during the first developmental transition.
  • Menin is also required for endocrine pancreas development during the second transition, impacting alpha- and beta-cell differentiation.
  • Menin plays an indispensable role throughout the development of pancreatic endocrine cells.

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