title: Neurogenin3 initiates stepwise delamination of differentiating endocrine cells during pancreas development.
abstract: 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.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Gouzi
authors.forename: Yung Hae
authors.initials: YH
authors.lastname: Kim
authors.forename: Keiichi
authors.initials: K
authors.lastname: Katsumoto
authors.forename: Kerstin
authors.initials: K
authors.lastname: Johansson
authors.forename: Anne
authors.initials: A
authors.lastname: Grapin-Botton
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology; D002642:Chick Embryo; D002645:Chickens; D018274:Electroporation; D005260:Female; D005455:Fluorescent Antibody Technique; D017403:In Situ Hybridization; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D009419:Nerve Tissue Proteins; C407737:Neurog3 protein, mouse