Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptional networks identify synaptotagmin-like 3 as a regulator of cortical neuronal migration during early neurodevelopment


ABSTRACT: Human brain development is a complex process involving neural proliferation, differentiation, and migration which are directed by many essential cellular factors and drivers. Here, using the NetBID2 algorithm and developing human brain RNA sequencing(RNA-Seq) dataset, we identified synaptotagmin-like 3(SYTL3) as one of the top drivers of early human brain development. Interestingly, SYTL3 exhibited 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 promoted neuronal migration. Besides, SYTL3-KO caused an abnormal distribution of deep-layer neurons in brain organoids and reduced presynaptic neurotransmitter release in hESC-derived neurons. We further demonstrated that SYTL3-KO- accelerated neuronal migration was modulated by high expression of matrix metalloproteinases. Together, based on bioinformatics and biological experiments, we identified SYTL3 as a novel regulator of cortical neuronal migration in human and mouse developing brains.

INSTRUMENT(S): HiSeq X Ten

ORGANISM(S): Homo sapiens

SUBMITTER: Xinran Dong 

PROVIDER: E-MTAB-10058 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcriptional networks identify synaptotagmin-like 3 as a regulator of cortical neuronal migration during early neurodevelopment.

Dong Xinran X   Yang Lin L   Liu Kaiyi K   Ji Xiaoli X   Tang Chuanqing C   Li Wanxing W   Ma Ling L   Mei Yuting Y   Peng Ting T   Feng Ban B   Wu Ziyan Z   Tang Qingyuan Q   Gao Yanyan Y   Yan Kai K   Zhou Wenhao W   Xiong Man M  

Cell reports 20210301 9


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)  ...[more]

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