| Summary: | 博士 === 國立成功大學 === 生物資訊與訊息傳遞研究所 === 102 === Leave or die, is a serious task for differentiating cells. During neuronal differentiation, cells need to be well-equipped for differentiation process. Gene expressions and cytoskeleton reorganizations are necessary for neuronal differentiation, but most important thing is to depart form cell cycle at the right time. Fail to exit cell cycle in time fires cell cycle-related neuronal death, eliminating cells which are not ready for neuronal differentiation. Brain finger protein, Znf179 was known to express predominantly in brain, and the expression significantly increased during embryogenesis, suggesting the potential role of Znf179 in neuronal development. In this study, we demonstrated that Znf179 expression increased gradually during P19 cells neuronal differentiation. Inhibition of Znf179 expression by RNA interference dramatically suppressed the neuronal differentiation of both P19 and primary cerebellar granular cells. By using microarray technique and functional annotation analysis, we identified the differentially expressed genes in Znf179-knockdown cells, and found that those genes were mostly involved in development, cell proliferation and cell cycle regulation. In our results, cell cycle arrest for neuronal differentiation was abolished in Znf179-knockdown cells. First, flow cytometry indicated the reduced population of G0/G1 phase in Znf179-knockdown cells. Second, BrdU-incorporated cells were also increased upon Znf179 knockdown. Moreover, in Znf179-knockdown cells, p35, which was known to activate CDK5 and may alter the cell cycle, and p27, a cell cycle inhibitor, were also decreased. Taken together, these lines of evidence showed that the induction of Znf179 may be related to p35 expression and p27 protein accumulation, which allowed cell cycle arrest in the G0/G1 phase, and was critical for neuronal differentiation of P19 cells.
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