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

KA Johansson, U Dursun, N Jordan, G Gu… - Developmental cell, 2007 - cell.com
KA Johansson, U Dursun, N Jordan, G Gu, F Beermann, G Gradwohl, A Grapin-Botton
Developmental cell, 2007cell.com
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 …
Summary
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-ERTM 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.
cell.com