SP8 和 SP9 通过激活 表达协调促进 D2 型中型多棘神经元的产生。
SP8 and SP9 coordinately promote D2-type medium spiny neuron production by activating expression.
机构信息
State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA.
出版信息
Development. 2018 Jul 23;145(14):dev165456. doi: 10.1242/dev.165456.
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 and 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 in a spatially restricted domain of the LGE subventricular zone. Conditional deletion of also prevents the formation of most D2 MSNs, phenocopying the mutants. Finally, ChIP-Seq reveals that SP9 directly binds to the promoter and a putative enhancer of Thus, this study defines components of a transcription pathway in a regionally restricted LGE progenitor domain that selectively drives the generation of D2 MSNs.
DRD1 表达的多巴胺受体中间神经元（D1 MSNs）和 DRD2 表达的多巴胺受体中间神经元（D2 MSNs）是纹状体中的主要投射神经元，纹状体分为背侧纹状体（尾状核和壳核）和腹侧纹状体（伏隔核和嗅结节）。这些神经元的前体细胞来源于外侧神经节隆起（LGE）。通过条件性缺失，我们发现缺乏转录因子基因 和 的小鼠由于 LGE 中的神经发生减少而几乎失去了所有的 D2 MSNs，而 D1 MSNs 则基本不受影响。SP8 和 SP9 共同驱动转录因子 在 LGE 室下区的一个空间限制区域的表达。条件性缺失 也阻止了大多数 D2 MSNs 的形成，表现出与 突变体相似的表型。最后，ChIP-Seq 揭示 SP9 直接结合到 启动子和一个假定的增强子上。因此，这项研究定义了一个在区域限制的 LGE 祖细胞区域中选择性驱动 D2 MSNs 生成的转录途径的组成部分。
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