title: Cell cycle progression is required for zebrafish somite morphogenesis but not segmentation clock function.
abstract: Cell division, differentiation and morphogenesis are coordinated during embryonic development, and frequently are in disarray in pathologies such as cancer. Here, we present a zebrafish mutant that ceases mitosis at the beginning of gastrulation, but that undergoes axis elongation and develops blood, muscle and a beating heart. We identify the mutation as being in early mitotic inhibitor 1 (emi1), a negative regulator of the Anaphase Promoting Complex, and use the mutant to examine the role of the cell cycle in somitogenesis. The mutant phenotype indicates that axis elongation during the segmentation period is driven substantially by cell migration. We find that the segmentation clock, which regulates somitogenesis, functions normally in the absence of cell cycle progression, and observe that mitosis is a modest source of noise for the clock. Somite morphogenesis involves the epithelialization of the somite border cells around a core of mesenchyme. As in wild-type embryos, somite boundary cells are polarized along a Fibronectin matrix in emi1(-/-). The mutants also display evidence of segment polarity. However, in the absence of a normal cell cycle, somites appear to hyper-epithelialize, as the internal mesenchymal cells exit the core of the somite after initial boundary formation. Thus, cell cycle progression is not required during the segmentation period for segmentation clock function but is necessary for the normal segmental arrangement of epithelial borders and internal mesenchymal cells.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
authors.forename: Lixia
authors.initials: L
authors.lastname: Zhang
authors.forename: Christina
authors.initials: C
authors.lastname: Kendrick
authors.forename: Dörthe
authors.initials: D
authors.lastname: Jülich
authors.forename: Scott A
authors.initials: SA
authors.lastname: Holley
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000502:physiology; D009024:Morphogenesis; D009154:Mutation; D019170:Somites / Q000166:cytology / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D029961:Zebrafish Proteins; C530717:fbxo5 protein, zebrafish