AUTHOR=Shang Zicong , Yang Lin , Wang Ziwu , Tian Yu , Gao Yanjing , Su Zihao , Guo Rongliang , Li Weiwei , Liu Guoping , Li Xiaosu , Yang Zhengang , Li Zhenmeiyu , Zhang Zhuangzhi 

TITLE=The transcription factor Zfp503 promotes the D1 MSN identity and represses the D2 MSN identity

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.948331

DOI=10.3389/fcell.2022.948331

ISSN=2296-634X

ABSTRACT=<p>The striatum is primarily composed of two types of medium spiny neurons (MSNs) expressing either D1- or D2-type dopamine receptors. However, the fate determination of these two types of neurons is not fully understood. Here, we found that D1 MSNs undergo fate switching to D2 MSNs in the absence of <italic>Zfp503</italic>. Furthermore, scRNA-seq revealed that the transcription factor <italic>Zfp503</italic> affects the differentiation of these progenitor cells in the lateral ganglionic eminence (LGE). More importantly, we found that the transcription factors <italic>Sp8/9</italic>, which are required for the differentiation of D2 MSNs, are repressed by <italic>Zfp503</italic>. Finally, sustained <italic>Zfp503</italic> expression in LGE progenitor cells promoted the D1 MSN identity and repressed the D2 MSN identity. Overall, our findings indicated that <italic>Zfp503</italic> promotes the D1 MSN identity and represses the D2 MSN identity by regulating <italic>Sp8/9</italic> expression during striatal MSN development.</p>