Back to Search
Start Over
neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2000 Feb 15; Vol. 97 (4), pp. 1607-11. - Publication Year :
- 2000
-
Abstract
- In the mammalian pancreas, the endocrine cell types of the islets of Langerhans, including the alpha-, beta-, delta-, and pancreatic polypeptide cells as well as the exocrine cells, derive from foregut endodermal progenitors. Recent genetic studies have identified a network of transcription factors, including Pdx1, Isl1, Pax4, Pax6, NeuroD, Nkx2.2, and Hlxb9, regulating the development of islet cells at different stages, but the molecular mechanisms controlling the specification of pancreatic endocrine precursors remain unknown. neurogenin3 (ngn3) is a member of a family of basic helix-loop-helix transcription factors that is involved in the determination of neural precursor cells in the neuroectoderm. ngn3 is expressed in discrete regions of the nervous system and in scattered cells in the embryonic pancreas. We show herein that ngn3-positive cells coexpress neither insulin nor glucagon, suggesting that ngn3 marks early precursors of pancreatic endocrine cells. Mice lacking ngn3 function fail to generate any pancreatic endocrine cells and die postnatally from diabetes. Expression of Isl1, Pax4, Pax6, and NeuroD is lost, and endocrine precursors are lacking in the mutant pancreatic epithelium. Thus, ngn3 is required for the specification of a common precursor for the four pancreatic endocrine cell types.
- Subjects :
- Animals
Basic Helix-Loop-Helix Transcription Factors
Cell Differentiation drug effects
DNA-Binding Proteins metabolism
Embryonic and Fetal Development
Eye Proteins
Glucagon metabolism
Helix-Loop-Helix Motifs
Histocytochemistry
Homeobox Protein Nkx-2.2
Homeodomain Proteins metabolism
In Situ Hybridization
In Situ Nick-End Labeling
Insulin metabolism
Mice
Mice, Knockout
Nerve Tissue Proteins metabolism
PAX6 Transcription Factor
Paired Box Transcription Factors
RNA, Messenger metabolism
Repressor Proteins
Somatostatin metabolism
Trans-Activators metabolism
Islets of Langerhans embryology
Nerve Tissue Proteins genetics
Pancreas embryology
Transcription Factors metabolism
Xenopus Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 97
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 10677506
- Full Text :
- https://doi.org/10.1073/pnas.97.4.1607