title: Tumor suppressor Lzap regulates cell cycle progression, doming, and zebrafish epiboly.
abstract: Initial stages of embryonic development rely on rapid, synchronized cell divisions of the fertilized egg followed by a set of morphogenetic movements collectively called epiboly and gastrulation. Lzap is a putative tumor suppressor whose expression is lost in 30% of head and neck squamous cell carcinomas. Lzap activities include regulation of cell cycle progression and response to therapeutic agents. Here, we explore developmental roles of the lzap gene during zebrafish morphogenesis. Lzap is highly conserved among vertebrates and is maternally deposited. Expression is initially ubiquitous during gastrulation, and later becomes more prominent in the pharyngeal arches, digestive tract, and brain. Antisense morpholino-mediated depletion of Lzap resulted in delayed cell divisions and apoptosis during blastomere formation, resulting in fewer, larger cells. Cell cycle analysis suggested that Lzap loss in early embryonic cells resulted in a G2/M arrest. Furthermore, the Lzap-deficient embryos failed to initiate epiboly--the earliest morphogenetic movement in animal development--which has been shown to be dependent on cell adhesion and migration of epithelial sheets. Our results strongly implicate Lzap in regulation of cell cycle progression, adhesion and migratory activity of epithelial cell sheets during early development. These functions provide further insight into Lzap activity that may contribute not only to development, but also to tumor formation.
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Wen-Der
authors.initials: WD
authors.lastname: Wang
authors.forename: David B
authors.initials: DB
authors.lastname: Melville
authors.forename: Yong I
authors.initials: YI
authors.lastname: Cha
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Yin
authors.forename: Natalia
authors.initials: N
authors.lastname: Issaeva
authors.forename: Ela W
authors.initials: EW
authors.lastname: Knapik
authors.forename: Wendell G
authors.initials: WG
authors.lastname: Yarbrough
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002453:Cell Cycle / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics*; D004625:Embryo, Nonmammalian; D016147:Genes, Tumor Suppressor / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C561480:CDK5Rap3 protein, zebrafish; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins