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Publication : The nuclear lamina couples mechanical forces to cell fate in the preimplantation embryo via actin organization.

First Author  Skory RM Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  3101
PubMed ID  37248263 Mgi Jnum  J:336153
Mgi Id  MGI:7487439 Doi  10.1038/s41467-023-38770-5
Citation  Skory RM, et al. (2023) The nuclear lamina couples mechanical forces to cell fate in the preimplantation embryo via actin organization. Nat Commun 14(1):3101
abstractText  During preimplantation development, contractile forces generated at the apical cortex segregate cells into inner and outer positions of the embryo, establishing the inner cell mass (ICM) and trophectoderm. To which extent these forces influence ICM-trophectoderm fate remains unresolved. Here, we found that the nuclear lamina is coupled to the cortex via an F-actin meshwork in mouse and human embryos. Actomyosin contractility increases during development, upregulating Lamin-A levels, but upon internalization cells lose their apical cortex and downregulate Lamin-A. Low Lamin-A shifts the localization of actin nucleators from nucleus to cytoplasm increasing cytoplasmic F-actin abundance. This results in stabilization of Amot, Yap phosphorylation and acquisition of ICM over trophectoderm fate. By contrast, in outer cells, Lamin-A levels increase with contractility. This prevents Yap phosphorylation enabling Cdx2 to specify the trophectoderm. Thus, forces transmitted to the nuclear lamina control actin organization to differentially regulate the factors specifying lineage identity.
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