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Rett syndrome (RTT) is a severe neurodevelopmental disorder.Recently,mutations in X-linked cyclin-dependent kinase-like 5 (CDKL5,previously named STK9) have been identified in patients with early seizure variant of RTT.The clinical features of CDKL5 mutations suggest that CDKL5 plays important role in brain development.Here we show that CDKL5 is critical for dendrite development.CDKL5 is highly expressed in the developing brain.The distribution of CDKL5 mRNA and protein is correlated with the development and maturation of dendrites.Knocking down CDKL5 using RNA interference at early stages in cultured hippocampal neurons suppressed the growth of dendrites,while at late stages,when complex dendrites have already been established,knocking down CDKL5 caused the retraction of dendrites.These results demonstrate that CDKL5 is required for dendrite development and maintenance in primary cultured neurons and indicate that it may be important for dendrite morphogenesis in the brain.