Transcriptional networks identify synaptotagmin-like 3 as a regulator of cortical neuronal migration during early neurodevelopment
Transcriptional networks identify synaptotagmin-like 3 as a regulator of cortical neuronal migration during early neurodevelopment
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DOI：
10.1016/j.celrep.2021.108802
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发表时间：
2021-03-02
期刊：
影响因子：
8.8
通讯作者：
Xiong, Man
中科院分区：
文献类型：
--
作者：
Dong, Xinran;Yang, Lin;Xiong, Man
人脑发育是一个复杂的过程，涉及神经的增殖、分化和迁移，这些过程由许多基本的细胞因子和驱动因素指导。在这里，使用NetBID2算法和开发人脑RNA测序数据集，我们发现synaptopagmin-like 3(SYTL3)是人类早期大脑发育的顶级驱动因素之一。有趣的是，SYTL3在早期发育的人类皮质和人类胚胎干细胞(HESC)来源的神经元中显示出高活性但低表达。在人类神经元中敲除SYTL3(SYTL3-KO)或在胚胎小鼠皮质中敲除Sytl3显著促进神经元迁移。SYTL3-KO导致脑器体内深层神经元异常分布，减少hESC来源神经元突触前递质的释放。我们进一步证明，SYTL3-KO加速的神经元迁移是由基质金属蛋白酶的高表达所调节的。总之，基于生物信息学和生物学实验，我们确定SYTL3是发育中的人和小鼠大脑皮质神经元迁移的调节因子。
Human brain development is a complex process involving neural proliferation, differentiation, and migration that are directed by many essential cellular factors and drivers. Here, using the NetBID2 algorithm and developing human brain RNA sequencing dataset, we identify synaptotagmin-like 3 (SYTL3) as one of the top drivers of early human brain development. Interestingly, SYTL3 exhibits high activity but low expression in both early developmental human cortex and human embryonic stem cell (hESC)-derived neurons. Knockout of SYTL3 (SYTL3-KO) in human neurons or knockdown of Sytl3 in embryonic mouse cortex markedly promotes neuronal migration. SYTL3-KO causes an abnormal distribution of deep-layer neurons in brain organoids and reduces presynaptic neurotransmitter release in hESC-derived neurons. We further demonstrate that SYTL3-KO-accelerated neuronal migration is modulated by high expression of matrix metalloproteinases. Together, based on bioinformatics and biological experiments, we identify SYTL3 as a regulator of cortical neuronal migration in human and mouse developing brains.