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Gene Review

Neurog3  -  neurogenin 3

Mus musculus

Synonyms: Ath4b, Atoh5, Helix-loop-helix protein mATH-4B, Math4B, NGN-3, ...
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Disease relevance of Neurog3


High impact information on Neurog3

  • Biliary epithelium in Hes1-/- mice ectopically expresses the proendocrine gene Neurog3 (refs. 12,13), differentiates into endocrine and exocrine cells and forms acini and islet-like structures in the mutant bile ducts [3].
  • In these embryos, expression of Isl1 and Atoh5, essential regulators of pancreatic morphogenesis and differentiation, was severely reduced [4].
  • These data provide evidence that ngn3 acts as proendocrine gene and that Notch signalling is critical for the decision between the endocrine and progenitor/exocrine fates in the developing pancreas [5].
  • One such transcription factor, Arx, exhibits Ngn3-dependent expression throughout endocrine pancreas development in alpha, beta-precursor, and delta cells [6].
  • Thus, ngn3 is required for the differentiation of enteroendocrine cells in the stomach and the maintenance of gastric epithelial cell identity [1].

Biological context of Neurog3


Anatomical context of Neurog3


Associations of Neurog3 with chemical compounds

  • PDX-1/VP16 fusion protein, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance [12].
  • Furthermore, in streptozotocin-induced diabetic mice, PDX-1/VP16 overexpression, together with NeuroD or Ngn3, drastically ameliorated glucose tolerance [12].

Co-localisations of Neurog3

  • Sox3 expression was restricted to proliferating germ cells and colocalized with neurogenin 3 (Ngn3), a helix-loop-helix transcription factor implicated in spermatogonial differentiation [13].

Regulatory relationships of Neurog3

  • We show herein that ngn3-positive cells coexpress neither insulin nor glucagon, suggesting that ngn3 marks early precursors of pancreatic endocrine cells [14].
  • However, embryos lacking Ngn3 fail to express IA1 in the pancreas [7].
  • Furthermore, endocrine differentiation is associated with escape from this activity, because Ngn3-expressing endocrine precursors are susceptible to Notch inhibition, whereas fully differentiated endocrine cells are resistant [15].
  • Gdf11 is expressed in embryonic pancreatic epithelium during formation of islet progenitor cells that express neurogenin 3 [16].
  • We showed previously that the Onecut transcription factor HNF-6 promotes differentiation of the endocrine cell precursors in which it stimulates expression of the proendocrine gene Ngn-3 [17].

Other interactions of Neurog3


Analytical, diagnostic and therapeutic context of Neurog3

  • To understand the molecular basis of enteroendocrine cell development, we have used gene targeting in mouse embryonic stem cells to derive an EGFP-marked null allele of the bHLH transcription factor, neurogenin 3 (ngn3) [1].
  • The purified (96%) EGFP-expressing cells, which represent 20% of the total cell population, were shown by RT/PCR to express exocrine cell markers (amylase and P48) and endocrine cell markers (insulin 1, insulin 2, and Ngn3) [20].
  • Genomic Southern blot hybridization suggested that a closely related sequence is present in the zebrafish genome and the hypothetical gene might result from the recent genome duplication in certain teleost lineage and share the function of the common ancestor with the currently characterized ngn3 [21].
  • Using degenerate PCR, the P. obesus Neurogenin-3 (Ngn-3) gene was cloned [22].


  1. Neurogenin 3 is essential for the proper specification of gastric enteroendocrine cells and the maintenance of gastric epithelial cell identity. Lee, C.S., Perreault, N., Brestelli, J.E., Kaestner, K.H. Genes Dev. (2002) [Pubmed]
  2. Adenovirus Transduction is Required for the Correction of Diabetes Using Pdx-1 or Neurogenin-3 in the Liver. Wang, A.Y., Ehrhardt, A., Xu, H., Kay, M.A. Mol. Ther. (2007) [Pubmed]
  3. Conversion of biliary system to pancreatic tissue in Hes1-deficient mice. Sumazaki, R., Shiojiri, N., Isoyama, S., Masu, M., Keino-Masu, K., Osawa, M., Nakauchi, H., Kageyama, R., Matsui, A. Nat. Genet. (2004) [Pubmed]
  4. Pbx1 inactivation disrupts pancreas development and in Ipf1-deficient mice promotes diabetes mellitus. Kim, S.K., Selleri, L., Lee, J.S., Zhang, A.Y., Gu, X., Jacobs, Y., Cleary, M.L. Nat. Genet. (2002) [Pubmed]
  5. Notch signalling controls pancreatic cell differentiation. Apelqvist, A., Li, H., Sommer, L., Beatus, P., Anderson, D.J., Honjo, T., Hrabe de Angelis, M., Lendahl, U., Edlund, H. Nature (1999) [Pubmed]
  6. Opposing actions of Arx and Pax4 in endocrine pancreas development. Collombat, P., Mansouri, A., Hecksher-Sorensen, J., Serup, P., Krull, J., Gradwohl, G., Gruss, P. Genes Dev. (2003) [Pubmed]
  7. IA1 is NGN3-dependent and essential for differentiation of the endocrine pancreas. Mellitzer, G., Bonné, S., Luco, R.F., Van De Casteele, M., Lenne-Samuel, N., Collombat, P., Mansouri, A., Lee, J., Lan, M., Pipeleers, D., Nielsen, F.C., Ferrer, J., Gradwohl, G., Heimberg, H. EMBO J. (2006) [Pubmed]
  8. Regeneration of pancreatic islets after partial pancreatectomy in mice does not involve the reactivation of neurogenin-3. Lee, C.S., De León, D.D., Kaestner, K.H., Stoffers, D.A. Diabetes (2006) [Pubmed]
  9. Neurogenin 3 and the enteroendocrine cell lineage in the adult mouse small intestinal epithelium. Bjerknes, M., Cheng, H. Dev. Biol. (2006) [Pubmed]
  10. Neurogenin3 is differentially required for endocrine cell fate specification in the intestinal and gastric epithelium. Jenny, M., Uhl, C., Roche, C., Duluc, I., Guillermin, V., Guillemot, F., Jensen, J., Kedinger, M., Gradwohl, G. EMBO J. (2002) [Pubmed]
  11. Regulation of the pancreatic islet-specific gene BETA2 (neuroD) by neurogenin 3. Huang, H.P., Liu, M., El-Hodiri, H.M., Chu, K., Jamrich, M., Tsai, M.J. Mol. Cell. Biol. (2000) [Pubmed]
  12. PDX-1/VP16 fusion protein, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. Kaneto, H., Nakatani, Y., Miyatsuka, T., Matsuoka, T.A., Matsuhisa, M., Hori, M., Yamasaki, Y. Diabetes (2005) [Pubmed]
  13. Sox3 expression in undifferentiated spermatogonia is required for the progression of spermatogenesis. Raverot, G., Weiss, J., Park, S.Y., Hurley, L., Jameson, J.L. Dev. Biol. (2005) [Pubmed]
  14. neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Gradwohl, G., Dierich, A., LeMeur, M., Guillemot, F. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  15. Notch signaling controls multiple steps of pancreatic differentiation. Murtaugh, L.C., Stanger, B.Z., Kwan, K.M., Melton, D.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  16. GDF11 modulates NGN3+ islet progenitor cell number and promotes beta-cell differentiation in pancreas development. Harmon, E.B., Apelqvist, A.A., Smart, N.G., Gu, X., Osborne, D.H., Kim, S.K. Development (2004) [Pubmed]
  17. The Onecut transcription factor HNF-6 (OC-1) is required for timely specification of the pancreas and acts upstream of Pdx-1 in the specification cascade. Jacquemin, P., Lemaigre, F.P., Rousseau, G.G. Dev. Biol. (2003) [Pubmed]
  18. Expression in murine teratocarcinoma F9 cells of transcription factors involved in pancreas development. O'Driscoll, L., Gammell, P., Clynes, M. Transplant. Proc. (2004) [Pubmed]
  19. Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell domain of the embryonic pancreas. Maestro, M.A., Boj, S.F., Luco, R.F., Pierreux, C.E., Cabedo, J., Servitja, J.M., German, M.S., Rousseau, G.G., Lemaigre, F.P., Ferrer, J. Hum. Mol. Genet. (2003) [Pubmed]
  20. Presence of endocrine and exocrine markers in EGFP-positive cells from the developing pancreas of a nestin/EGFP mouse. Bernardo, A.S., Barrow, J., Hay, C.W., McCreath, K., Kind, A.J., Schnieke, A.E., Colman, A., Hart, A.W., Docherty, K. Mol. Cell. Endocrinol. (2006) [Pubmed]
  21. A novel zebrafish bHLH gene, neurogenin3, is expressed in the hypothalamus. Wang, X., Chu, L.T., He, J., Emelyanov, A., Korzh, V., Gong, Z. Gene (2001) [Pubmed]
  22. Developmental Biology of the Psammomys obesus Pancreas: Cloning and Expression of the Neurogenin-3 Gene. Vedtofte, L., B??dvarsd??ttir, T.B., Karlsen, A.E., Heller, R.S. J. Histochem. Cytochem. (2007) [Pubmed]
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