先天性小头畸形为临床可识别的脑发育异常重要表现之一，与神经系统预后不良相关。小头畸形患儿常伴有脑白质发育不良，少突胶质细胞是脑白质固有细胞之一，其发育障碍可引起不同程度小头畸形。本课题组前期在157例先天性小头畸形的全外显子家系分析中发现其新的候选基因CTDNEP1基因；动物模型发现神经干细胞中特异性敲除Ctdnep1基因的小鼠生后具有小头畸形表现；在少突胶质细胞系中特异性敲除Ctdnep1基因的小鼠髓鞘发育明显受损，由此推测，CTDNEP1参与调控少突胶质细胞发育分化和髓鞘形成，其异常可导致小头畸形发生。本课题拟利用Ctdnep1条件性敲除小鼠模型，观察CTDNEP1在正常发育和病理状态下对少突胶质细胞分化和髓鞘形成的影响；通过RNA测序和生物信息分析寻找其下游调控基因和信号通路，从而探讨CTDNEP1在中枢神经系统发育、髓鞘形成和再生中的分子机制，为治疗白质损伤性疾病提供新的治疗策略。

Congenital microcephaly is one of the most visual manifestations of brain developmental abnormalities. Clarifying the etiology and pathogenesis of microcephaly timely plays a significant role in improving the prognosis of patients. Cerebral white matter hypoplasia usually can be found in the patients with microcephaly. Myelin abnormalities and loss of pre-oligodendrocyte cell processes occurring in cerebral white matter hypoplasia suggested the necessity to understand the underlying mechanisms promoting effective (re)myelination. Molecular mechanisms underlying oligodendrocyte myelination and remyelination are poorly understood. Our previous study showed that the mice with Ctdnep1 conditional knockout in neural stem cells had declined survival rate and presented with microcephaly. To identify whether the microcephaly is due to the developmental abnormalities of oligodendrocytes, we have Ctdnep1 conditional knockout in oligodendrocytes. The mice showed myelin dysplasia and reduced proliferation of oligodendrocytes. This study intends to make use of the Ctdnep1-mutant strains to decipher the development of central nervous system, myelination and remyelination, which may prosper the treatment strategies for myelin dysplasia and microcephaly.