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

Zhenmeiyu Li; Zicong Shang; Mengge Sun; Xin Jiang; Yu Tian; Lin Yang; Ziwu Wang; Zihao Su; Guoping Liu; Xiaosu li; Yan You; Zhengang Yang; Zhejun Xu; Zhuangzhi Zhang

doi:10.1038/s41420-022-01088-0

Cell Death Discovery (Jun 2022)

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

Zhenmeiyu Li,
Zicong Shang,
Mengge Sun,
Xin Jiang,
Yu Tian,
Lin Yang,
Ziwu Wang,
Zihao Su,
Guoping Liu,
Xiaosu li,
Yan You,
Zhengang Yang,
Zhejun Xu,
Zhuangzhi Zhang

Affiliations

Zhenmeiyu Li: Institute of Pediatrics, Children’s Hospital of Fudan University, state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University
Zicong Shang: Institute of Pediatrics, Children’s Hospital of Fudan University, state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University
Mengge Sun: Institute of Pediatrics, Children’s Hospital of Fudan University, state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University
Xin Jiang: Institute of Pediatrics, Children’s Hospital of Fudan University, state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University
Yu Tian: Institute of Pediatrics, Children’s Hospital of Fudan University, state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University
Lin Yang: Institute of Pediatrics, Children’s Hospital of Fudan University, state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University
Ziwu Wang: Institute of Pediatrics, Children’s Hospital of Fudan University, state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University
Zihao Su: Institute of Pediatrics, Children’s Hospital of Fudan University, state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University
Guoping Liu: Institute of Pediatrics, Children’s Hospital of Fudan University, state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University
Xiaosu li: Institute of Pediatrics, Children’s Hospital of Fudan University, state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University
Yan You: Institute of Pediatrics, Children’s Hospital of Fudan University, state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University
Zhengang Yang: Institute of Pediatrics, Children’s Hospital of Fudan University, state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University
Zhejun Xu: Institute of Pediatrics, Children’s Hospital of Fudan University, state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University
Zhuangzhi Zhang: Institute of Pediatrics, Children’s Hospital of Fudan University, state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University

DOI: https://doi.org/10.1038/s41420-022-01088-0
Journal volume & issue: Vol. 8, no. 1
pp. 1 – 12

Abstract

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Abstract 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.

Published in Cell Death Discovery

ISSN: 2058-7716 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Science: Biology (General): Cytology
Website: http://www.nature.com/cddiscovery/

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