The CTNNBIP1-CLSTN1 fusion transcript regulates human neocortical development.
Autor: | Ou MY; 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., Xiao Q; 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., Ju XC; Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: xiangchun.ju@oist.jp., Zeng PM; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Huang J; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Sheng AL; Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China., Luo ZG; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. Electronic address: luozhg@shanghaitech.edu.cn. |
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Jazyk: | angličtina |
Zdroj: | Cell reports [Cell Rep] 2021 Jun 29; Vol. 35 (13), pp. 109290. |
DOI: | 10.1016/j.celrep.2021.109290 |
Abstrakt: | 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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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