Temporal control of neurogenin3 activity in pancreas progenitors reveals competence windows for the generation of different endocrine cell types.

Johansson KA, Dursun U, Jordan N, Gu G, Beermann F, Gradwohl G, Grapin-Botton A
Dev Cell. 2007 12 (3): 457-65

PMID: 17336910 · DOI:10.1016/j.devcel.2007.02.010

All pancreatic endocrine cells, producing glucagon, insulin, somatostatin, or PP, differentiate from Pdx1+ progenitors that transiently express Neurogenin3. To understand whether the competence of pancreatic progenitors changes over time, we generated transgenic mice expressing a tamoxifen-inducible Ngn3 fusion protein under the control of the pdx1 promoter and backcrossed the transgene into the ngn3(-/-) background, devoid of endogenous endocrine cells. Early activation of Ngn3-ER(TM) almost exclusively induced glucagon+ cells, while depleting the pool of pancreas progenitors. As from E11.5, Pdx1+ progenitors became competent to differentiate into insulin+ and PP+ cells. Somatostatin+ cells were generated from E14.5, while the competence to make glucagon+ cells was dramatically decreased. Hence, pancreas progenitors, similar to retinal or cortical progenitors, go through competence states that each allow the generation of a subset of cell types. We further show that the progenitors acquire competence to generate late-born cells in a mechanism that is intrinsic to the epithelium.

MeSH Terms (23)

Animals Basic Helix-Loop-Helix Transcription Factors Cell Differentiation Endocrine System Epithelial Cells Female Gene Expression Regulation, Developmental Glucagon Homeodomain Proteins Insulin Insulin Secretion Islets of Langerhans Male Mice Mice, Knockout Nerve Tissue Proteins Pancreas Pancreatic Hormones Promoter Regions, Genetic Somatostatin Stem Cells Time Factors Trans-Activators

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