The role of NPRL2 and NPRL3 in neural development and disorders

• Main Authors: Ssu-Yu Yeh, 葉思妤
• Other Authors: Jin-Wu Tsai
• Format: Others
• Language: en_US
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/g7542n

碩士 === 國立陽明大學 === 腦科學研究所 === 107 === The neurodevelopmental disorder focal cortical dysplasia (FCD) is the most common cause of medically refractory epilepsy in both children. Several genes have been identified to be involved in the pathogenesis of this disease, including NPRL2, NPRL3 and DEPDC5, the components of GATOR1 complex. GATOR1 complex acts as a negative regulator of mTORC1 in mTOR signaling pathway, which regulates cell growth, metabolism, autophagy, and proliferation. Although mutations in these genes have been reported to cause FCD and focal epilepsy, the functions of NPRL2/3 in neural development is still not fully understood. To investigate the roles of NPRL2/3 in cortical development, we delivered shRNA by in utero electroporation (IUE) to knock down NPRL2/3 in neural progenitors of mouse embryos. We found that NPRL2/3 knockdown during development caused neuronal migration delay. Furthermore, we observed dendritic morphological changes in the NPRL2/3-knockdown neurons in postnatal mice. Meanwhile, we identified potential novel mutations on NPRL2 and NPRL3 in patients with focal epilepsy. To study whether these mutations will cause neuronal defects or not, we electroporated wild type or mutant NPRL2/3 into mouse embryonic neural progenitors. However, expression of both mutant and wildtype NPRL2 did not cause apparent neural migration defects. Our study may help us understand the roles of NPRL2/3 in neuronal development and provide information for developing effective treatment to NRRL2/3-related neural developmental disorders.