title: The cfy mutation disrupts cell divisions in a stage-dependent manner in zebrafish embryos.
abstract: The zebrafish curly fry (cfy) mutation leads to embryonic lethality and abnormal cell divisions starting at 12-14 h postfertilization (hpf) during neural tube formation. The mitotic defect is seen in a variety of tissues including the central nervous system (CNS). In homozygous mutant embryos, mitoses are disorganized with an increase in mitotic figures throughout the developing neural tube. One consequence of aberrant mitoses in cfy embryos is an increase in cell death. Despite this, patterning of the early CNS is relatively unperturbed with distribution of the early, primary neurons indistinguishable from that of wild-type embryos. At later stages, however, the number of neurons was dramatically decreased throughout the CNS. The effect on neurons in older cfy embryos but not young ones correlates with the time of birth of neurons: primary neurons are born before the action of the cfy gene and later neurons after. Presumably, death of neuronal progenitors that divide beginning at the neural keel stage or death of their neuronal progeny accounts for the diminution of neurons in older mutant embryos. In addition, oligodendrocytes, which also develop late in the CNS, are greatly reduced in number in cfy embryos due to an apparent decrease in oligodendrocyte precursors. Genetic mosaic analysis demonstrates that the mutant phenotype is cell-autonomous. Furthermore, there are no obvious defects in apical/basal polarity within the neuroepithelium, suggesting that the cfy gene is not critical for epithelial polarity and that polarity defects are unlikely to account for the increased mitotic figures in mutants. These results suggest that the cfy gene regulates mitosis perhaps in a stage-dependent manner in vertebrate embryos.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
authors.forename: Mi Hye
authors.initials: MH
authors.lastname: Song
authors.forename: Nadean L
authors.initials: NL
authors.lastname: Brown
authors.forename: John Y
authors.initials: JY
authors.lastname: Kuwada
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D016923:Cell Death; D002455:Cell Division / Q000235:genetics*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D006720:Homozygote; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009030:Mosaicism / Q000196:embryology; D009154:Mutation; D009474:Neurons / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology; D013194:Staining and Labeling; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D029961:Zebrafish Proteins