Institute of Neuroscience, CAS Key Laboratory of Primate Neurobiology, State Kay Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai, 200031, China.
Department of Neonatology, Children's Hospital of Fudan University, Shanghai, 201102, China.
Sci Rep. 2017 Jan 31;7:41701. doi: 10.1038/srep41701.
Duplications of Methyl CpG binding protein 2 (MECP2) -containing segments lead to the MECP2 duplication syndrome, in which severe autistic symptoms were identified. Whether adult neurogenesis may play a role in pathogenesis of autism and the role of MECP2 on state determination of adult neural stem cells (NSCs) remain largely unclear. Using a MECP2 transgenic (TG) mouse model for the MECP2 duplication syndrome, we found that adult hippocampal quiescent NSCs were significantly accumulated in TG mice comparing to wild type (WT) mice, the neural progenitor cells (NPCs) were reduced and the neuroblasts were increased in adult hippocampi of MECP2 TG mice. Interestingly, we found that parvalbumin (PV) positive interneurons were significantly decreased in MECP2 TG mice, which were critical for determining fates of adult hippocampal NSCs between the quiescence and activation. In summary, we found that MeCP2 plays a critical role in regulating fate determination of adult NSCs. These evidences further suggest that abnormal development of NSCs may play a role in the pathogenesis of the MECP2 duplication syndrome.
MECP2 基因重复片段的复制会导致 MECP2 重复综合征，这种综合征表现出严重的自闭症症状。目前尚不清楚成年神经发生是否在自闭症的发病机制中起作用，以及 MECP2 对成年神经干细胞（NSCs）状态决定的作用。我们使用 MECP2 转基因（TG）小鼠模型来模拟 MECP2 重复综合征，发现与野生型（WT）小鼠相比，成年海马静止 NSCs 在 TG 小鼠中明显积累，神经祖细胞（NPCs）减少，神经母细胞增加。有趣的是，我们发现 MECP2 TG 小鼠中 PV 阳性中间神经元显著减少，而这些神经元对于决定成年海马 NSCs 在静止和激活之间的命运至关重要。总之，我们发现 MeCP2 在调节成年 NSCs 的命运决定中起着关键作用。这些证据进一步表明，NSCs 的异常发育可能在 MECP2 重复综合征的发病机制中起作用。
