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Keratins are asymmetrically inherited fate determinants in the mammalian embryo

Author

Listed:
  • Hui Yi Grace Lim

    (Institute of Molecular and Cell Biology, ASTAR)

  • Yanina D. Alvarez

    (Institute of Molecular and Cell Biology, ASTAR)

  • Maxime Gasnier

    (Institute of Molecular and Cell Biology, ASTAR)

  • Yiming Wang

    (Institute of Zoology, Chinese Academy of Science)

  • Piotr Tetlak

    (Institute of Molecular and Cell Biology, ASTAR)

  • Stephanie Bissiere

    (Institute of Molecular and Cell Biology, ASTAR)

  • Hongmei Wang

    (Institute of Zoology, Chinese Academy of Science)

  • Maté Biro

    (University of New South Wales)

  • Nicolas Plachta

    (Institute of Molecular and Cell Biology, ASTAR
    University of Pennsylvania)

Abstract

To implant in the uterus, the mammalian embryo first specifies two cell lineages: the pluripotent inner cell mass that forms the fetus, and the outer trophectoderm layer that forms the placenta1. In many organisms, asymmetrically inherited fate determinants drive lineage specification2, but this is not thought to be the case during early mammalian development. Here we show that intermediate filaments assembled by keratins function as asymmetrically inherited fate determinants in the mammalian embryo. Unlike F-actin or microtubules, keratins are the first major components of the cytoskeleton that display prominent cell-to-cell variability, triggered by heterogeneities in the BAF chromatin-remodelling complex. Live-embryo imaging shows that keratins become asymmetrically inherited by outer daughter cells during cell division, where they stabilize the cortex to promote apical polarization and YAP-dependent expression of CDX2, thereby specifying the first trophectoderm cells of the embryo. Together, our data reveal a mechanism by which cell-to-cell heterogeneities that appear before the segregation of the trophectoderm and the inner cell mass influence lineage fate, via differential keratin regulation, and identify an early function for intermediate filaments in development.

Suggested Citation

  • Hui Yi Grace Lim & Yanina D. Alvarez & Maxime Gasnier & Yiming Wang & Piotr Tetlak & Stephanie Bissiere & Hongmei Wang & Maté Biro & Nicolas Plachta, 2020. "Keratins are asymmetrically inherited fate determinants in the mammalian embryo," Nature, Nature, vol. 585(7825), pages 404-409, September.
    • Handle: RePEc:nat:nature:v:585:y:2020:i:7825:d:10.1038_s41586-020-2647-4
    DOI: 10.1038/s41586-020-2647-4
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    Cited by:

    1. Junko Otsuki & Toshiroh Iwasaki & Noritoshi Enatsu & Yuya Katada & Kohyu Furuhashi & Masahide Shiotani, 2020. "The inclusion of blastomeres into the inner cell mass in early-stage human embryos depends on the sequence of cell cleavages during the fourth division," PLOS ONE, Public Library of Science, vol. 15(10), pages 1-7, October.
    2. Özge Özgüç & Ludmilla de Plater & Varun Kapoor & Anna Francesca Tortorelli & Andrew G Clark & Jean-Léon Maître, 2022. "Cortical softening elicits zygotic contractility during mouse preimplantation development," PLOS Biology, Public Library of Science, vol. 20(3), pages 1-23, March.

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