The CTNNBIP1-CLSTN1 fusion transcript regulates human neocortical development
Autor: | Peng-Ming Zeng, Xiang-Chun Ju, Jing Huang, Qi Xiao, Zhen-Ge Luo, Ai-Li Sheng, Min-Yi Ou |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
cortical expansion QH301-705.5 Down-Regulation Neocortex Biology General Biochemistry Genetics and Molecular Biology CTNNBIP1-CLSTN1 Cell Line 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Neural Stem Cells medicine Organoid Humans fusion transcript RNA Messenger Biology (General) Wnt Signaling Pathway beta Catenin Adaptor Proteins Signal Transducing Base Sequence Neurogenesis basal neural progenitor Wnt signaling pathway outer radial glia Human brain Embryonic stem cell Cell biology Organoids neurogenesis 030104 developmental biology medicine.anatomical_structure Fusion transcript Neuroglia 030217 neurology & neurosurgery Wnt/β-catenin signaling |
Zdroj: | Cell Reports, Vol 35, Iss 13, Pp 109290-(2021) |
ISSN: | 2211-1247 |
Popis: | 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. |
Databáze: | OpenAIRE |
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