title: Developmental defects observed in hypomorphic anaphase-promoting complex mutants are linked to cell cycle abnormalities.
abstract: In C. elegans, mutants in the anaphase-promoting complex or cyclosome (APC/C) exhibit defects in germline proliferation, the formation of the vulva and male tail, and the metaphase to anaphase transition of meiosis I. Oocytes lacking APC/C activity can be fertilized but arrest in metaphase of meiosis I and are blocked from further development. To examine the cell cycle and developmental consequences of reducing but not fully depleting APC/C activity, we analyzed defects in embryos and larvae of mat-1/cdc-27 mutants grown at semi-permissive temperatures. Hypomorphic embryos developed to the multicellular stage but were slow to complete meiosis I and displayed aberrant meiotic chromosome separation. More severely affected embryos skipped meiosis II altogether and exhibited striking defects in meiotic exit. These latter embryos failed to produce normal eggshells or establish normal asymmetries prior to the first mitotic division. In developing larvae, extended M-phase delays in late-dividing cell lineages were associated with defects in the morphogenesis of the male tail. This study reveals the importance of dosage-specific mutants in analyzing molecular functions of a ubiquitously functioning protein within different cell types and tissues, and striking correlations between specific abnormalities in cell cycle progression and particular developmental defects.
authors.affiliation: Department of Biology, College of William and Mary, Williamsburg, Virginia 23187, USA. dcshak@wm.edu
authors.forename: Diane C
authors.initials: DC
authors.lastname: Shakes
authors.forename: Penny L
authors.initials: PL
authors.lastname: Sadler
authors.forename: Jill M
authors.initials: JM
authors.lastname: Schumacher
authors.forename: Maziar
authors.initials: M
authors.lastname: Abdolrasulnia
authors.forename: Andy
authors.initials: A
authors.lastname: Golden
mesh_terms: D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000254:growth & development*; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D012734:Disorders of Sex Development; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology*; D007814:Larva / Q000033:anatomy & histology / Q000502:physiology*; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009024:Morphogenesis; D010641:Phenotype; D034622:RNA Interference; D016415:Sequence Alignment; D013696:Temperature; D019076:Transgenes; D043743:Ubiquitin-Protein Ligase Complexes
chemical_list: D018797:Cell Cycle Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D008025:Ligases