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Neurogenin3 initiates stepwise delamination of differentiating endocrine cells during pancreas development
Author(s) -
Gouzi Mathieu,
Kim Yung Hae,
Katsumoto Keiichi,
Johansson Kerstin,
GrapinBotton Anne
Publication year - 2011
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.22544
Subject(s) - biology , enteroendocrine cell , epithelium , progenitor cell , microbiology and biotechnology , endocrine system , mesenchyme , pancreas , medicine , endocrinology , progenitor , cadherin , stem cell , mesenchymal stem cell , cell , hormone , genetics
During development, pancreatic endocrine cells are specified within the pancreatic epithelium. They subsequently delaminate out of the epithelium and cluster in the mesenchyme to form the islets of Langerhans. Neurogenin3 (Ngn3) is a transcription factor required for the differentiation of all endocrine cells and we investigated its role in their delamination. We observed in the mouse pancreas that most Ngn3‐positive cells have lost contact with the lumen of the epithelium, showing that the delamination from the progenitor layer is initiated in endocrine progenitors. Subsequently, in both mouse and chick newly born endocrine cells at the periphery of the epithelium strongly decrease E‐cadherin, break‐down the basal lamina and cluster into islets of Langerhans. Repression of E‐cadherin is sufficient to promote delamination from the epithelium. We further demonstrate that Ngn3 indirectly controls Snail2 protein expression post‐transcriptionally to repress E‐cadherin. In the chick embryo, Ngn3 independently controls epithelium delamination and differentiation programs. Developmental Dynamics 240:589–604, 2011. © 2011 Wiley‐Liss, Inc.