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 PMID:29967281  

SP8 and SP9 coordinately promote D2-type medium spiny neuron production by activating Six3 expression.

Zhejun Xu | Qifei Liang | Xiaolei Song | Zhuangzhi Zhang | Susan Lindtner | Zhenmeiyu Li | Yan Wen | Guoping Liu | Teng Guo | Dashi Qi | Min Wang | Chunyang Wang | Hao Li | Yan You | Xin Wang | Bin Chen | Hua Feng | John L Rubenstein | Zhengang Yang
Development (Cambridge, England) | 2018

Dopamine receptor DRD1-expressing medium spiny neurons (D1 MSNs) and dopamine receptor DRD2-expressing medium spiny neurons (D2 MSNs) are the principal projection neurons in the striatum, which is divided into dorsal striatum (caudate nucleus and putamen) and ventral striatum (nucleus accumbens and olfactory tubercle). Progenitors of these neurons arise in the lateral ganglionic eminence (LGE). Using conditional deletion, we show that mice lacking the transcription factor genes Sp8 and Sp9 lose virtually all D2 MSNs as a result of reduced neurogenesis in the LGE, whereas D1 MSNs are largely unaffected. SP8 and SP9 together drive expression of the transcription factor Six3 in a spatially restricted domain of the LGE subventricular zone. Conditional deletion of Six3 also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 mutants. Finally, ChIP-Seq reveals that SP9 directly binds to the promoter and a putative enhancer of Six3 Thus, this study defines components of a transcription pathway in a regionally restricted LGE progenitor domain that selectively drives the generation of D2 MSNs.

Pubmed ID: 29967281

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Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: R01 MH049428
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH094589
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS089777
  • Agency: NIMH NIH HHS, United States
    Id: R37 MH049428

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Mutant Mouse Resource and Research Center (biomaterial supply resource)

RRID:SCR_002953

National public repository system for mutant mice. Archives and distributes scientifically valuable spontaneous and induced mutant mouse strains and ES cell lines for use by biomedical research community. Includes breeding/distribution facilities and information coordinating center. Mice strains are cryopreserved, unless live colony must be established. Live mice are supplied from production colony, from colony recovered from cryopreservation, or via micro-injection of cell line into host blastocysts. MMRRC member facilities also develop technologies to improve handling of mutant mice, including advances in assisted reproductive techniques, cryobiology, genetic analysis, phenotyping and infectious disease diagnostics.

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