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

• 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

SummaryStriatal 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 AbstractFigure optionsDownload as PowerPoint slide