Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 24, Pages 9715-9720Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0904247106
Keywords
endocrine progenitor; maintenance; pancreas; diabetes; sugar metabolism
Categories
Funding
- National Institutes of Health [DK065949, DK072473, DK072495, DK68471]
- Juvenile Diabetes Research Foundation [2007-712, 3-2004-608]
- Juvenile Diabetes Research Foundation
- European Union 6th Framework Program
- Danish Research Counsel [271-05-0667]
- Carlsberg Foundation
- Julie von Mullens fund
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Neurog3 (Neurogenin 3 or Ngn3) is both necessary and sufficient to induce endocrine islet cell differentiation from embryonic pancreatic progenitors. Since robust Neurog3 expression has not been detected in hormone-expressing cells, Neurog3 is used as an endocrine progenitor marker and regarded as dispensable for the function of differentiated islet cells. Here we used 3 independent lines of Neurog3 knock-in reporter mice and mRNA/protein-based assays to examine Neurog3 expression in hormone-expressing islet cells. Neurog3 mRNA and protein are detected in hormone-producing cells at both embryonic and adult stages. Significantly, inactivating Neurog3 in insulin-expressing beta cells at embryonic stages or in Pdx1-expressing islet cells in adults impairs endocrine function, a phenotype that is accompanied by reduced expression of several Neurog3 target genes that are essential for islet cell differentiation, maturation, and function. These findings demonstrate that Neurog3 is required not only for initiating endocrine cell differentiation, but also for promoting islet cell maturation and maintaining islet function.
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