The Zinc Finger Transcription Factor Sp9 Is Required for the Development of Striatopallidal Projection Neurons
Qiangqiang Zhang,
Yue Zhang,
Chunyang Wang,
Zhejun Xu,
Qifei Liang,
Lei An,
Jiwen Li,
Zhidong Liu,
Yan You,
Miao He,
Ying Mao,
Bin Chen,
Zhi-Qi Xiong,
John L. Rubenstein,
Zhengang Yang
Affiliations
Qiangqiang Zhang
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
Yue Zhang
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
Chunyang Wang
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
Zhejun Xu
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
Qifei Liang
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
Lei An
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
Jiwen Li
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
Zhidong Liu
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
Yan You
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
Miao He
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
Ying Mao
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
Bin Chen
Department of Molecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, CA 95064, USA
Zhi-Qi Xiong
Institute of Neuroscience, State Key Laboratory of Neuroscience, Chinese Academy of Sciences Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
John L. Rubenstein
Department of Psychiatry, Neuroscience Program and Nina Ireland Laboratory of Developmental Neurobiology, University of California San Francisco, San Francisco, CA 94158, USA
Zhengang Yang
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
Striatal medium-sized spiny neurons (MSNs), composed of striatonigral and striatopallidal neurons, are derived from the lateral ganglionic eminence (LGE). We find that the transcription factor Sp9 is expressed in LGE progenitors that generate nearly all striatal MSNs and that Sp9 expression is maintained in postmitotic striatopallidal MSNs. Sp9-null mice lose most striatopallidal MSNs because of decreased proliferation of striatopallidal MSN progenitors and increased Bax-dependent apoptosis, whereas the development of striatonigral neurons is largely unaffected. ChIP qPCR provides evidence that Ascl1 directly binds the Sp9 promoter. RNA-seq and in situ hybridization reveal that Sp9 promotes expression of Adora2a, P2ry1, Gpr6, and Grik3 in the LGE and striatum. Thus, Sp9 is crucial for the generation, differentiation, and survival of striatopallidal MSNs.
