Transcription factor Sp9 is a negative regulator of D1-type MSN development

• Published in: Cell death discovery Vol. 8; no. 1; p. 301
• Main Authors: Li, Zhenmeiyu, Shang, Zicong, Sun, Mengge, Jiang, Xin, Tian, Yu, Yang, Lin, Wang, Ziwu, Su, Zihao, Liu, Guoping, li, Xiaosu, You, Yan, Yang, Zhengang, Xu, Zhejun, Zhang, Zhuangzhi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.06.2022; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/378/2571; 631/378/87; Apoptosis; Basal ganglia; Biochemistry; Biomedical and Life Sciences; Blood; Cell Biology; Cell Cycle Analysis; Cognitive ability; Dopamine; Down-regulation; Gene expression; Genomics; Life Sciences; Motor task performance; Movement disorders; Neostriatum; Neurodegenerative diseases; Neuropeptides; Neurosciences; Parkinson's disease; Progenitor cells; Spiny neurons; Stem Cells; Thalamus; Transcription factors
• ISSN: 2058-7716; 2058-7716
• DOI: 10.1038/s41420-022-01088-0

The striatum is the main input structure of the basal ganglia, receiving information from the cortex and the thalamus and consisting of D1- and D2- medium spiny neurons (MSNs). D1-MSNs and D2-MSNs are essential for motor control and cognitive behaviors and have implications in Parkinson’s Disease. In the present study, we demonstrated that Sp9 -positive progenitors produced both D1-MSNs and D2-MSNs and that Sp9 expression was rapidly downregulated in postmitotic D1-MSNs. Furthermore, we found that sustained Sp9 expression in lateral ganglionic eminence (LGE) progenitor cells and their descendants led to promoting D2-MSN identity and repressing D1-MSN identity during striatal development. As a result, sustained Sp9 expression resulted in an imbalance between D1-MSNs and D2-MSNs in the mouse striatum. In addition, the fate-changed D2-like MSNs survived normally in adulthood. Taken together, our findings supported that Sp9 was sufficient to promote D2-MSN identity and repress D1-MSN identity, and Sp9 was a negative regulator of D1-MSN fate.