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Sustained Neurog3 expression in hormone-expressing islet cells is required for endocrine maturation and function.

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.

Pubmed ID: 19487660


  • Wang S
  • Jensen JN
  • Seymour PA
  • Hsu W
  • Dor Y
  • Sander M
  • Magnuson MA
  • Serup P
  • Gu G


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

June 16, 2009

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK065949
  • Agency: NIDDK NIH HHS, Id: DK072473
  • Agency: NIDDK NIH HHS, Id: DK072495
  • Agency: NIDDK NIH HHS, Id: DK68471
  • Agency: NCI NIH HHS, Id: R01 CA106308
  • Agency: NIDDK NIH HHS, Id: U01 DK072473

Mesh Terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Blotting, Western
  • Fluorescent Antibody Technique
  • Gene Knock-In Techniques
  • Glucose Tolerance Test
  • Immunohistochemistry
  • Insulin
  • Islets of Langerhans
  • Mice
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction