The CTNNBIP1-CLSTN1 fusion transcript regulates human neocortical development
Min-Yi Ou,
Qi Xiao,
Xiang-Chun Ju,
Peng-Ming Zeng,
Jing Huang,
Ai-Li Sheng,
Zhen-Ge Luo
Affiliations
Min-Yi Ou
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China
Qi Xiao
Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China
Xiang-Chun Ju
Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Corresponding author
Peng-Ming Zeng
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Jing Huang
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Ai-Li Sheng
Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Zhen-Ge Luo
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Corresponding author
Summary: Fusion transcripts or RNAs have been found in both disordered and healthy human tissues and cells; however, their physiological functions in the brain development remain unknown. In the analysis of deposited RNA-sequence libraries covering early to middle embryonic stages, we identify 1,055 fusion transcripts present in the developing neocortex. Interestingly, 98 fusion transcripts exhibit distinct expression patterns in various neural progenitors (NPs) or neurons. We focus on CTNNBIP1-CLSTN1 (CTCL), which is enriched in outer radial glial cells that contribute to cortex expansion during human evolution. Intriguingly, downregulation of CTCL in cultured human cerebral organoids causes marked reduction in NPs and precocious neuronal differentiation, leading to impairment of organoid growth. Furthermore, the expression of CTCL fine-tunes Wnt/β-catenin signaling that controls cortex patterning. Together, this work provides evidence indicating important roles of fusion transcript in human brain development and evolution.
