WDR81在成体神经发生过程中的作用与调控机制研究

Adult neurogenesis has been known to be involved in brain plasticity, learning and memory, and brain repair. Aberrant adult neurogenesis have been found in neurological disorders. Wdr81 has recently been described as the disease locus in a consanguineous family that suffers from cerebellar ataxia, mental retardation, and quadrupedal locomotion syndrome (CAMRQ). However, the pathological mechanisms that cause CAMRQ syndrome remain largely unknown. Our previous study shown that loss of WDR81 leads to aberrant adult neural stem cells proliferation and differentiation. Based on our previous findings, we aim to further investigate the underlying mechanism of WDR81 regulating adult neurogenesis by using adult neural stem cell lineage tracing, immunofluorescence, immunoprecipitation and behavioral assay. The proposed study will help us to understand the etiology of CAMRQ syndrome, and provide us a new therapeutic theory of prevention and intervention for treating this syndrome.

成体神经发生主要参与了大脑可塑性、学习记忆以及大脑的损伤修复。在神经疾病的研究中，均发现成体神经发生的异常。Wdr81 的突变导致小脑性共济失调，智力低下，和四足运动综合征 (CAMRQ syndrome) 。然而，Wdr81突变在CAMRQ综合征中的致病机制仍不清楚。我们的前期研究结果表明，WDR81的突变导致了成体神经干细胞增殖以及分化的异常。本项目将以此研究基础为切入点，运用成体神经干细胞谱系追踪、免疫荧光、免疫共沉淀以及动物行为学等实验手段，进一步研究WDR81调控成体神经发生的分子机制。此项目的研究结果将有助于我们了解CAMRQ综合征的发病机制，从而为这些疾病的预防和治疗提供理论基础。

成体神经发生主要参与了大脑可塑性、学习记忆以及大脑的损伤修复。在神经疾病的研究中，均发现成体神经发生的异常。WDR81 的突变导致小脑性共济失调，智力低下，和四足运动综合征 (CAMRQ2 syndrome) 。然而，WDR81突变在CAMRQ2综合征中的致病机制仍不清楚。通过在体神经干细胞谱系示踪、体外神经干细胞培养和免疫共沉淀等实验手段，发现WDR81通过SARA-TGFβ信号通路调控成体神经干细胞增殖分化，这一发现将有助于我们了解CAMRQ2综合征的发病机制，从而为这些疾病的预防和治疗提供理论基础。