Abstract
Development of endocrine cells in the endoderm involves Atonal and Achaete/Scute-related basic helix-loop-helix (bHLH) proteins. These proteins also serve as neuronal determination and differentiation factors, and are antagonized by the Notch pathway partly acting through Hairy and Enhancer-of-split (HES)-type proteins. Here we show that mice deficient in Hes1 (encoding Hes-1) display severe pancreatic hypoplasia caused by depletion of pancreatic epithelial precursors due to accelerated differentiation of post-mitotic endocrine cells expressing glucagon. Moreover, upregulation of several bHLH components is associated with precocious and excessive differentiation of multiple endocrine cell types in the developing stomach and gut, showing that Hes-1 operates as a general negative regulator of endodermal endocrine differentiation.
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Acknowledgements
We thank S. Saule, H. Edlund, J. Rehfeld, A. Buchanan, J. Habener and T. Sudo for antisera, and L. Flores, H.I. Jensen, R. Jørgensen, T. Funder-Nielsen and L. Heller for technical assistance. This work was supported by NIH grant DK-55284 and the Danish National Research Foundation. J.J. is a recipient of a fellowship from the Juvenile Diabetes Foundation International.
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Jensen, J., Pedersen, E., Galante, P. et al. Control of endodermal endocrine development by Hes-1. Nat Genet 24, 36–44 (2000). https://doi.org/10.1038/71657
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DOI: https://doi.org/10.1038/71657
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