title: Kif2a depletion generates chromosome segregation and pole coalescence defects in animal caps and inhibits gastrulation of the Xenopus embryo.
abstract: Kif2a is a member of the kinesin-13 microtubule depolymerases, which tightly regulate microtubule dynamics for many cellular processes. We characterized Kif2a depletion in Xenopus animal caps and embryos. Kif2a depletion generates defects in blastopore closure. These defects are rescued by removing the animal cap, suggesting that Kif2a-depleted animal caps are not compliant enough to allow gastrulation movements. Gastrulation defects are not rescued by a Kif2a mutated in an Aurora kinase phosphorylation site, suggesting that the phenotypes are caused by problems in mitosis. During animal cap mitoses, Kif2a localizes to the spindle poles and centromeres. Depletion of Kif2a generated multipolar spindles in stage 12 embryos. Kif2a-depleted animal caps have anaphase lagging chromosomes in stage 9 and 10 embryos and subsequent cytokinesis failure. Later divisions have greater than two centrosomes, generating extra spindle poles. Kif2a-depleted embryos are also defective at coalescing extra spindle poles into a bipolar spindle. The gastrulation and mitotic phenotypes can be rescued by either human Kif2a or Kif2b, which suggests that the two homologues redundantly regulate mitosis in mammals. These studies demonstrate that defects in mitosis can inhibit large-scale developmental movements in vertebrate tissues.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors.forename: Gerald
authors.initials: G
authors.lastname: Eagleson
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, VA 22904.
authors.forename: Katherine
authors.initials: K
authors.lastname: Pfister
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Knowlton
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, VA 22904.
authors.forename: Paul
authors.initials: P
authors.lastname: Skoglund
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, VA 22904.
authors.forename: Ray
authors.initials: R
authors.lastname: Keller
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908 pts7h@virginia.edu.
authors.forename: P Todd
authors.initials: PT
authors.lastname: Stukenberg
mesh_terms: D000818:Animals; D020090:Chromosome Segregation / Q000235:genetics*; D048749:Cytokinesis / Q000235:genetics; D015536:Down-Regulation; D054262:Gastrulation / Q000235:genetics*; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000502:physiology*; D064047:Spindle Poles / Q000235:genetics*; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: C509805:KIF2A protein, human; D029867:Xenopus Proteins; C522444:KIF2 protein, Xenopus; C523507:KIF2B protein, human; D016547:Kinesins