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.

Highlights

  • CDK10 is involved in cell proliferation; the function of CDK10 in cell development remains unclear

  • These results demonstrated that cdk10 interacts with ETS2 and are similar to the results obtained with human and murine CDK10

  • Recent studies suggested that human CDK10 functions as a tumor suppressor gene, preventing cell proliferation in breast cancer [12], biliary tract cancer cells [29], and hepatoma [30]

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Summary

Background

CDK10 is involved in cell proliferation; the function of CDK10 in cell development remains unclear. Conclusion: Zebrafish cdk exhibits an important function in neurogenesis by the modulation of the raf1a level during development. Morpholino-based loss of cdk 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 cdk morphants. This result is similar to that demonstrated by decreased islet expression in the dorsal regions. Knockdown of zebrafish cdk by using siRNA decreases the number of primary sensory Rohon-Beard (RB) neurons in the trigeminal ganglia and promotes apoptosis in the brain [15, 16]. We used zebrafish as an animal model to investigate the developmental role of cdk

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