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

• Main Authors: Jiang, X. (Author), li, X. (Author), Li, Z. (Author), Liu, G. (Author), Shang, Z. (Author), Su, Z. (Author), Sun, M. (Author), Tian, Y. (Author), Wang, Z. (Author), Xu, Z. (Author), Yang, L. (Author), Yang, Z. (Author), You, Y. (Author), Zhang, Z. (Author)
• Format: Article
• Language: English
• Published: Springer Nature 2022
• Online Access: View Fulltext in Publisher
• ISBN: 20587716 (ISSN)
• 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. © 2022, The Author(s).