Basal delamination during mouse gastrulation primes pluripotent cells for differentiation.

Autor: Sato N; MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK., Rosa VS; MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK., Makhlouf A; MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK., Kretzmer H; Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany., Sampath Kumar A; Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany., Grosswendt S; Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Max Delbruck Center for Molecular Medicine, 13125 Berlin, Germany; Berlin Institute of Health (BIH) at Charité-Universitätsmedizin, Berlin, Germany., Mattei AL; Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany., Courbot O; Cell and Tissue Mechanobiology Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Department of Physics, King's College London, London WC2R 2LS, UK., Wolf S; MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK., Boulanger J; MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK., Langevin F; MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK., Wiacek M; MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK., Karpinski D; MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK., Elosegui-Artola A; Cell and Tissue Mechanobiology Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Department of Physics, King's College London, London WC2R 2LS, UK., Meissner A; Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany., Zernicka-Goetz M; University of Cambridge, Cambridge CB2 3EL, UK; California Institute of Technology, Pasadena, CA 91125, USA., Shahbazi MN; MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. Electronic address: mshahbazi@mrc-lmb.cam.ac.uk.
Jazyk: angličtina
Zdroj: Developmental cell [Dev Cell] 2024 May 20; Vol. 59 (10), pp. 1252-1268.e13. Date of Electronic Publication: 2024 Apr 04.
DOI: 10.1016/j.devcel.2024.03.008
Abstrakt: The blueprint of the mammalian body plan is laid out during gastrulation, when a trilaminar embryo is formed. This process entails a burst of proliferation, the ingression of embryonic epiblast cells at the primitive streak, and their priming toward primitive streak fates. How these different events are coordinated remains unknown. Here, we developed and characterized a 3D culture of self-renewing mouse embryonic cells that captures the main transcriptional and architectural features of the early gastrulating mouse epiblast. Using this system in combination with microfabrication and in vivo experiments, we found that proliferation-induced crowding triggers delamination of cells that express high levels of the apical polarity protein aPKC. Upon delamination, cells become more sensitive to Wnt signaling and upregulate the expression of primitive streak markers such as Brachyury. This mechanistic coupling between ingression and differentiation ensures that the right cell types become specified at the right place during embryonic development.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 MRC Laboratory of Molecular Biology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE