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

Autor: Skory RM; Department of Cell and Developmental Biology, Institute for Regenerative Medicine Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Moverley AA; Department of Cell and Developmental Biology, Institute for Regenerative Medicine Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; University College London, WC1E 6BT, London, UK., Ardestani G; Boston IVF-Eugin Group, Waltham, MA, USA., Alvarez Y; Universidad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina., Domingo-Muelas A; Department of Cell and Developmental Biology, Institute for Regenerative Medicine Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Pomp O; Department of Cell and Developmental Biology, Institute for Regenerative Medicine Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Hernandez B; Department of Cell and Developmental Biology, Institute for Regenerative Medicine Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Tetlak P; Department of Cell and Developmental Biology, Institute for Regenerative Medicine Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Bissiere S; Department of Cell and Developmental Biology, Institute for Regenerative Medicine Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Stern CD; University College London, WC1E 6BT, London, UK., Sakkas D; Boston IVF-Eugin Group, Waltham, MA, USA. dsakkas@bostonivf.com., Plachta N; Department of Cell and Developmental Biology, Institute for Regenerative Medicine Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. nicolas.plachta@pennmedicine.upenn.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 May 29; Vol. 14 (1), pp. 3101. Date of Electronic Publication: 2023 May 29.
DOI: 10.1038/s41467-023-38770-5
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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