The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Regulation of the Pancreatic Pro-Endocrine Gene Neurogenin3
Abstract
Neurogenin3 (ngn3), a basic helix-loop-helix (bHLH) transcription factor, functions as a pro-endocrine factor in the developing pancreas: by itself, it is sufficient to force undifferentiated pancreatic epithelial cells to become islet cells. Because ngn3 expression determines which precursor cells will differentiate into islet cells, the signals that regulate ngn3 expression control islet cell formation. To investigate the factors that control ngn3 gene expression, we mapped the human and mouse ngn3 promoters and delineated transcriptionally active sequences within the human promoter. Surprisingly, the human ngn3 promoter drives transcription in all cell lines tested, including fibroblast cell lines. In contrast, in transgenic animals the promoter drives expression specifically in regions of ngn3 expression in the developing pancreas and gut; and the addition of distal sequences greatly enhances transgene expression. Within the distal enhancer, binding sites for several pancreatic transcription factors, including hepatocyte nuclear factor (HNF)-1 and HNF-3, form a tight cluster. HES1, an inhibitory bHLH factor activated by Notch signaling, binds to the proximal promoter and specifically blocks promoter activity. Together with previous genetic data, these results suggest a model in which the ngn3 gene is activated by the coordinated activities of several pancreatic transcription factors and inhibited by Notch signaling through HES1.
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Cites
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neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas
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Control of endodermal endocrine development by Hes-1
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Expression of neurogenin3 reveals an islet cell precursor population in the pancreas
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Cited by
β Cells Can Be Generated from Endogenous Progenitors in Injured Adult Mouse Pancreas
Xu, X., D'Hoker, J., Stangé, G., Bonné, S., De Leu, N., Xiao, X., Van De Casteele, M., Mellitzer, G., Ling, Z., Pipeleers, D., et al. (2008) · Cell · doi:10.1016/j.cell.2007.12.015 · Cited by 988
Notch signals control the fate of immature progenitor cells in the intestine
Fre, S., Huyghe, M., Mourikis, P., Robine, S., Louvard, D., & Artavanis-Tsakonas, S. (2005) · Nature · doi:10.1038/nature03589 · Cited by 935
Developmental biology of the pancreas: A comprehensive review
Gittes, G. K. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2008.10.024 · Cited by 451
MicroRNA Expression Is Required for Pancreatic Islet Cell Genesis in the Mouse
Lynn, F. C., Skewes-Cox, P., Kosaka, Y., McManus, M. T., Harfe, B. D., & German, M. S. (2007) · Diabetes · doi:10.2337/db07-0175 · Cited by 351
Self-citationMinireview: Development and Differentiation of Gut Endocrine Cells
Schonhoff, S. E., Giel-Moloney, M., & Leiter, A. B. (2004) · Endocrinology · doi:10.1210/en.2004-0051 · Cited by 322
Metadata
- Authors
- Lee, J. C., Smith, S. B., Watada, H., Lin, J., Scheel, D., Wang, J., Mirmira, R. G., & German, M. S.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2001-05-01
- Volume
- 50
- Issue
- 5
- Pages
- 928-936
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2162464438
- Cited by
- 257
- References
- 47
- FWCI
- 11.18
- Type
- journal article
- Language
- en
- Open access
- closed
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