ALBERT

Description: Publication date: Available online 21 July 2016 Source: Cell Reports Author(s): 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 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. Graphical abstract Teaser 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.