NEUROD1 Is Required for the Early alpha and beta Endocrine Differentiation in the Pancreas

0548733 - BTÚ 2022 RIV CH eng J - Journal Article
Bohuslavová, Romana - Smolík, Ondřej - Malfatti, Jessica - Berková, Z. - Nováková, Žaneta - Saudek, F. - Pavlínková, Gabriela
NEUROD1 Is Required for the Early alpha and beta Endocrine Differentiation in the Pancreas.
International Journal of Molecular Sciences. Roč. 22, č. 13 (2021). E-ISSN 1422-0067
R&D Projects: GA ČR(CZ) GA19-07378S
Institutional support: RVO:86652036
Keywords : transcriptional network * mouse model * pancreatic development
OECD category: Biochemistry and molecular biology
Impact factor: 6.208, year: 2021
Method of publishing: Open access
https://www.mdpi.com/1422-0067/22/13/6713

Diabetes is a metabolic disease that involves the death or dysfunction of the insulin-secreting beta cells in the pancreas. Consequently, most diabetes research is aimed at understanding the molecular and cellular bases of pancreatic development, islet formation, beta-cell survival, and insulin secretion. Complex interactions of signaling pathways and transcription factor networks regulate the specification, growth, and differentiation of cell types in the developing pancreas. Many of the same regulators continue to modulate gene expression and cell fate of the adult pancreas. The transcription factor NEUROD1 is essential for the maturation of beta cells and the expansion of the pancreatic islet cell mass. Mutations of the Neurod1 gene cause diabetes in humans and mice. However, the different aspects of the requirement of NEUROD1 for pancreas development are not fully understood. In this study, we investigated the role of NEUROD1 during the primary and secondary transitions of mouse pancreas development. We determined that the elimination of Neurod1 impairs the expression of key transcription factors for alpha- and beta-cell differentiation, beta-cell proliferation, insulin production, and islets of Langerhans formation. These findings demonstrate that the Neurod1 deletion altered the properties of alpha and beta endocrine cells, resulting in severe neonatal diabetes, and thus, NEUROD1 is required for proper activation of the transcriptional network and differentiation of functional alpha and beta cells.
Permanent Link: http://hdl.handle.net/11104/0324778