Genomics,Multiomics

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Sp8 and Sp9 Coordinately Promote Striatal Medium Spiny Neuron Production through Activating Six3 Expression

ABSTRACT: D1- and D2-type medium spiny neurons (MSNs) are the principal projection neurons in the striatum, including in the dorsal striatum (caudate nucleus and putamen) and ventral striatum (nucleus accumbens and olfactory tubercle) that are generated by the lateral ganglionic eminence (LGE). Using conditional deletion, we show that mice lacking the Sp8 and Sp9 transcription factors (TFs) selectively have a severe reduction in D2 MSNs due to reduced neurogenesis in the LGE. Sp8/9 together drive expression of the Six3 TF in a spatial restricted domain of the LGE subventricular zone. Conditional deletion of Six3 also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 loss of function. Finally, ChIP-Seq reveals that SP9 directly binds to the promoter and a putative enhancer of Six3. This study provides evidence for components of a transcription pathway, in a regionally restricted LGE domain, that selectively drives the generation of D2 MSNs.

SUBMITTER: hua,feng 

PROVIDER: OEX000045 | NODE |

REPOSITORIES: NODE

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

Xu Zhejun Z   Liang Qifei Q   Song Xiaolei X   Zhang Zhuangzhi Z   Lindtner Susan S   Li Zhenmeiyu Z   Wen Yan Y   Liu Guoping G   Guo Teng T   Qi Dashi D   Wang Min M   Wang Chunyang C   Li Hao H   You Yan Y   Wang Xin X   Chen Bin B   Feng Hua H   Rubenstein John L JL   Yang Zhengang Z  

Development (Cambridge, England) 20180723 14

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 <i>Sp8</i> and <i  ...[more]

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