SALL2 regulates neural differentiation of mouse embryonic stem cells through Tuba1a

The spalt (Sal) gene family has four members (Sall1-4) in vertebrates, all of which play pivotal roles in various biological processes and diseases. However, the expression and function of SALL2 in development are still less clear. Here, we first charted SALL2 protein expression pattern during mouse embryo development by immunofluorescence, which revealed its dominant expression in the developing nervous system. With the establishment of Sall2 deficient mouse embryonic stem cells (ESCs), the in vitro neural differentiation system was leveraged to interrogate the function of SALL2, which showed impaired neural differentiation of Sall2 knockout (KO) ESCs. Furthermore, neural stem cells (NSCs) could not be derived from Sall2 KO ESCs and the generation of neural tube organoids (NTOs) was greatly inhibited in the absence of SALL2. Meanwhile, transgenic expression of E1 isoform of SALL2 restored the defects of neural differentiation in Sall2 KO ESCs. By chromatin immunoprecipitation sequencing (ChIP-seq), Tuba1a was identified as downstream target of SALL2, whose function in neural differentiation was confirmed by rescuing neural phenotypes of Sall2 KO ESCs when overexpressed. In sum, by elucidating SALL2 expression dynamics during early mouse development and mechanistically characterizing its indispensable role in neural differentiation, this study offers insights into SALL2's function in human nervous system development, associated pathologies stemming from its mutations and relevant therapeutic strategy.

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Publication Details

Journal
Cell Death and Disease
Published
2024-09-30
DOI
https://doi.org/10.1038/s41419-024-07088-5
Citations
1
Primary Topic
Renal and related cancers
Type
article
Field-Weighted Citation Impact
0.23

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article

SALL2 regulates neural differentiation of mouse embryonic stem cells through Tuba1a

Duanyang Xie, Wenjun Liu, Mingshuai Zhang, Zhen Liu et al.
1 citations
Cell Death and Disease
Renal and related cancers
0.23
article

SALL2 regulates neural differentiation of mouse embryonic stem cells through Tuba1a

Duanyang Xie, Wenjun Liu, Mingshuai Zhang, Zhen Liu, Hui Xiong, Jie Ding, Chengwen Hang, Dan Shi, Dandan Liang, Zheng Gong, Zheyi Lin, Jian Yang, Lei Zhang, Bowen Lin, Renhong Lu, Yihan Chen, Junyang Liu, Huixin Guo, Yi Liu, Siyu Wang
article en
1 citations

Abstract

The spalt (Sal) gene family has four members (Sall1-4) in vertebrates, all of which play pivotal roles in various biological processes and diseases. However, the expression and function of SALL2 in development are still less clear. Here, we first charted SALL2 protein expression pattern during mouse embryo development by immunofluorescence, which revealed its dominant expression in the developing nervous system. With the establishment of Sall2 deficient mouse embryonic stem cells (ESCs), the in vitro neural differentiation system was leveraged to interrogate the function of SALL2, which showed impaired neural differentiation of Sall2 knockout (KO) ESCs. Furthermore, neural stem cells (NSCs) could not be derived from Sall2 KO ESCs and the generation of neural tube organoids (NTOs) was greatly inhibited in the absence of SALL2. Meanwhile, transgenic expression of E1 isoform of SALL2 restored the defects of neural differentiation in Sall2 KO ESCs. By chromatin immunoprecipitation sequencing (ChIP-seq), Tuba1a was identified as downstream target of SALL2, whose function in neural differentiation was confirmed by rescuing neural phenotypes of Sall2 KO ESCs when overexpressed. In sum, by elucidating SALL2 expression dynamics during early mouse development and mechanistically characterizing its indispensable role in neural differentiation, this study offers insights into SALL2's function in human nervous system development, associated pathologies stemming from its mutations and relevant therapeutic strategy.

Cell Death and DiseaseVol. 15(9)
Tongji University (CN), Heart Rhythm Society (US), Shanxi Medical University (CN), Chinese Academy of Sciences (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Center for Excellence in Brain Science and Intelligence Technology (CN), Shanghai East Hospital (CN), Second Hospital of Shanxi Medical University (CN), Shanghai Center for Brain Science and Brain-Inspired Technology (CN), University of Chinese Academy of Sciences (CN), State Key Laboratory of Cardiovascular Disease, Jinzhou Medical University (CN)
National Natural Science Foundation of China, Zhejiang University, Chinese Academy of Medical Sciences, Fundamental Research Funds for the Central Universities
Openalex Percentile: Top 42%
Renal and related cancers
0.23
DOIOpen Access PDFOpenAlex
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