SP8 and SP9 coordinately promote D2-type medium spiny neuron production by activating <i>Six3</i> expression
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- Zhejun Xu
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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- Qifei Liang
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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- Xiaolei Song
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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- Zhuangzhi Zhang
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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- Susan Lindtner
- Nina Ireland Laboratory of Developmental Neurobiology, UCSF Weill Institute for Neurosciences, University of California 2 Department of Psychiatry , , San Francisco, CA 94158 , USA
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- Zhenmeiyu Li
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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- Yan Wen
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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- Guoping Liu
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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- Teng Guo
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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- Dashi Qi
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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- Min Wang
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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- Chunyang Wang
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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- Hao Li
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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- Yan You
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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- Xin Wang
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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- Bin Chen
- University of California 3 Department of Molecular, Cell and Developmental Biology , , Santa Cruz, CA 95064 , USA
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- Hua Feng
- CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 4 CAS Key Laboratory of Computational Biology , , Shanghai 200031 , China
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- John L. Rubenstein
- Nina Ireland Laboratory of Developmental Neurobiology, UCSF Weill Institute for Neurosciences, University of California 2 Department of Psychiatry , , San Francisco, CA 94158 , USA
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- Zhengang Yang
- Institutes of Brain Science 1 State Key Laboratory of Medical Neurobiology , , Department of Neurology , , Shanghai 200032 , China
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<jats:title>ABSTRACT</jats:title> <jats:p>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.</jats:p>
収録刊行物
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- Development
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Development 145 (14), dev165456-, 2018-07-15
The Company of Biologists
