title: Knockdown of cyclin-dependent kinase 10 (cdk10) gene impairs neural progenitor survival via modulation of raf1a gene expression.
abstract: In this study, we used zebrafish as an animal model to elucidate the developmental function of cdk10 in vertebrates. In situ hybridization analyses demonstrated that cdk10 is expressed throughout development with a relative enrichment in the brain in the late stages. Similar to its mammalian ortholog, cdk10 can interact with the transcription factor ETS2 and exhibit kinase activity by phosphorylating histone H1. Morpholino-based loss of cdk10 expression caused apoptosis in sox2-positive cells and decreased the expression of subsequent neuronal markers. Acetylated tubulin staining revealed a significant reduction in the number of Rohon-Beard sensory neurons in cdk10 morphants. This result is similar to that demonstrated by decreased islet2 expression in the dorsal regions. Moreover, cdk10 morphants exhibited a marked loss of huC-positive neurons in the telencephalon and throughout the spinal cord axis. The population of retinal ganglion cells was also diminished in cdk10 morphants. These phenotypes were rescued by co-injection of cdk10 mRNA. Interestingly, the knockdown of cdk10 significantly elevated raf1a mRNA expression. Meanwhile, an MEK inhibitor (U0126) recovered sox2 and ngn1 transcript levels in cdk10 morphants. Our findings provide the first functional characterization of cdk10 in vertebrate development and reveal its critical function in neurogenesis by modulation of raf1a expression.
authors.affiliation: From the Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung City 40201, Taiwan.
authors.forename: Chi-Wei
authors.initials: CW
authors.lastname: Yeh
authors.forename: Shoa-Hsuan
authors.initials: SH
authors.lastname: Kao
authors.forename: Yi-Chuan
authors.initials: YC
authors.lastname: Cheng
authors.forename: Li-Sung
authors.initials: LS
authors.lastname: Hsu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology; D017386:Sequence Homology, Amino Acid; D013234:Stem Cells / Q000166:cytology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D029961:Zebrafish Proteins; D019908:Proto-Oncogene Proteins c-raf; C501013:CDK10 protein, human; C585171:CDK10 protein, zebrafish; C501014:Cdk10 protein, mouse; D018844:Cyclin-Dependent Kinases
keywords: Apoptosis; CDK (Cyclin-dependent Kinase); Development; Neurons; Zebrafish; cdk10
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