The Zinc Finger Transcription Factor Sp9 Is Required for the Development of Striatopallidal Projection Neurons

• Published in: Cell reports (Cambridge) 2016-08, Vol.16 (5), p.1431-1444
• Main Authors: Zhang, Qiangqiang, Zhang, Yue, Wang, Chunyang, Xu, Zhejun, Liang, Qifei, An, Lei, Li, Jiwen, Liu, Zhidong, You, Yan, He, Miao, Mao, Ying, Chen, Bin, Xiong, Zhi-Qi, Rubenstein, John L., Yang, Zhengang
• Format: Article
• Language: English
• Subjects: Adora2a; Animals; Apoptosis - genetics; Apoptosis - physiology; Ascl1; Cell Differentiation - genetics; Cell Differentiation - physiology; Cell Proliferation - genetics; Cell Proliferation - physiology; Corpus Striatum - metabolism; Corpus Striatum - physiology; Drd2; Gene Expression - genetics; Gene Expression - physiology; LGE; Mice; Mice, Knockout; Neurons - metabolism; Neurons - physiology; Promoter Regions, Genetic - genetics; Sp9; striatopallidal neuron; striatum; Substantia Nigra - metabolism; Substantia Nigra - physiology; Transcription Factors - genetics; Transcription Factors - metabolism; Zinc Fingers - genetics
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.06.090

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. [Display omitted] •Sp9 promotes striatopallidal MSN progenitor division and differentiation•Sp9 is required for the survival of striatopallidal MSNs•Ascl1 directly regulates the Sp9 promoter in vivo•Sp9 promotes Adora2a, P2ry1, Gpr6, and Grik3 expression in the striatum Zhang et al. analyze Sp9 constitutive and conditional knockout mice and find that this zinc finger transcription factor is critical for the proliferation, differentiation, and survival of striatopallidal projection neurons. The development of striatonigral projection neurons is, in contrast, largely unaffected by the absence of Sp9.