title: Micronucleus formation causes perpetual unilateral chromosome inheritance in mouse embryos.
abstract: Chromosome segregation defects in cancer cells lead to encapsulation of chromosomes in micronuclei (MN), small nucleus-like structures within which dangerous DNA rearrangements termed chromothripsis can occur. Here we uncover a strikingly different consequence of MN formation in preimplantation development. We find that chromosomes from within MN become damaged and fail to support a functional kinetochore. MN are therefore not segregated, but are instead inherited by one of the two daughter cells. We find that the same MN can be inherited several times without rejoining the principal nucleus and without altering the kinetics of cell divisions. MN motion is passive, resulting in an even distribution of MN across the first two cell lineages. We propose that perpetual unilateral MN inheritance constitutes an unexpected mode of chromosome missegregation, which could contribute to the high frequency of aneuploid cells in mammalian embryos, but simultaneously may serve to insulate the early embryonic genome from chromothripsis.
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal H2X 0A9, Québec, Canada;
authors.forename: Cayetana
authors.initials: C
authors.lastname: Vázquez-Diez
authors.affiliation: Faculty of Biology-Oriented Science and Technology, Kinki University, Kinokawa City, Wakayama, Japan 649-6493;
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamagata
authors.affiliation: Department of Cell and Developmental Biology, University College London, WC1E 6BT, United Kingdom;
authors.forename: Shardul
authors.initials: S
authors.lastname: Trivedi
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal H2X 0A9, Québec, Canada;
authors.forename: Jenna
authors.initials: J
authors.lastname: Haverfield
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal H2X 0A9, Québec, Canada; Departement d'obstétrique-gynécologie, Université de Montréal, Montréal H3T 1C5, Québec, Canada greg.fitzharris@umontreal.ca.
authors.forename: Greg
authors.initials: G
authors.lastname: FitzHarris
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D002455:Cell Division; D048430:Cell Shape; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004622:Embryo, Mammalian / Q000378:metabolism*; D047108:Embryonic Development; D005260:Female; D021621:Imaging, Three-Dimensional; D040582:Inheritance Patterns / Q000235:genetics*; D018386:Kinetochores; D008297:Male; D008677:Metaphase; D051379:Mice; D048631:Micronucleus, Germline / Q000378:metabolism*; D008954:Models, Biological; D011003:Ploidies
keywords: chromosome segregation; embryo mosaicism; micronuclei; mitosis; preimplantation development