脆性X综合征是由RNA结合蛋白Fmrp表达缺失引起的，并最终导致大脑神经发育的缺陷。然而，Fmrp调控神经发育的分子机制仍然不清楚。长非编码RNA（lncRNA）在神经发育中起了重要作用。但是，Fmrp与lncRNA神经发育过程中相互作用的研究目前仍未见报道。我们前期的研究结果表明，Fmrp的缺失导致成体新生神经元形体发生的异常，并且Fmrp能够结合并调控lncRNA Tug1的表达。这一发现提示我们，Fmrp可能通过调控lncRNA的表达进而影响神经元形体发生。本项目将以此研究基础为切入点，运用在体逆转录病毒注射、“透明脑”、RNA-IP和qRT-PCR等实验手段进一步研究Fmrp通过调控lncRNA 的表达以及Fmrp与lncRNA互作在调控神经元形态发生中分子机制。此项目的研究结果将有助于我们了解脆性X综合征的发病机制，并为该疾病的预防和治疗提供新的理论依据。

Fragile X syndrome is caused by the functional loss of RNA binding protein, fragile x mental retardation protein (Fmrp), which leads to neurodevelopmental deficiency in the brain. How Fmrp regulate neuronal development is not well understood. Long non-coding RNA (lncRNA) plays an important role in neuronal development. How Fmrp control neuronal development through lncRNA has not been reported. Our previous study shows Fmrp deficiency leads to neuronal morphogenesis deficits of adult newborn neurons, and Fmrp binds to lncRNA Tug1 and regulates its expression, which suggested that Fmrp may control neuronal morphogenesis through regulating lncRNA. Based on previous findings, we aim to further investigate the molecular mechanisms of how Fmrp regulate the expression of lncRNA and the functional role of the interaction of Fmrp and lncRNA on the neuronal morphogenesis by using in vivo retro-virus delivery, “CLARITY” technology, RNA-immunprecipitation and qRT-PCR. The proposed study will help us to understand the etiology of fragile X syndrome, and provide us a new therapeutic theory of prevention and intervention for treating fragile X syndrome.