Abstract: Diabetes is a metabolic disease that involves the death or dysfunction of the insulinsecreting cells in the pancreas. Consequently, most diabetes research is aimed at understanding themolecular and cellular bases of pancreatic development, islet formation, -cell survival, and insulinsecretion. Complex interactions of signaling pathways and transcription factor networks regulate thespecification, growth, and differentiation of cell types in the developing pancreas. Many of the sameregulators continue to modulate gene expression and cell fate of the adult pancreas. The transcriptionfactor NEUROD1 is essential for the maturation of cells and the expansion of the pancreatic isletcell mass. Mutations of the Neurod1 gene cause diabetes in humans and mice. However, the differentaspects of the requirement of NEUROD1 for pancreas development are not fully understood. In thisstudy, we investigated the role of NEUROD1 during the primary and secondary transitions of mousepancreas development. We determined that the elimination of Neurod1 impairs the expression of keytranscription factors for - and -cell differentiation, -cell proliferation, insulin production, andislets of Langerhans formation. These findings demonstrate that the Neurod1 deletion altered theproperties of and endocrine cells, resulting in severe neonatal diabetes, and thus, NEUROD1is required for proper activation of the transcriptional network and differentiation of functionaland cells.
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