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Your search keyword '"John L. Rubenstein"' showing total 2 results
Start Over Author "John L. Rubenstein" Topic dna-binding proteins
2 results on '"John L. Rubenstein"'

1. Dlx1/2-dependent expression of Meis2 promotes neuronal fate determination in the mammalian striatum

Author

Zihao Su, Ziwu Wang, Susan Lindtner, Lin Yang, Zicong Shang, Yu Tian, Rongliang Guo, Yan You, Wenhao Zhou, John L. Rubenstein, Zhengang Yang, and Zhuangzhi Zhang

Subjects
Homeodomain Proteins, Neurons, Neurogenesis, Intracellular Signaling Peptides and Proteins, Mice, Transgenic, Nerve Tissue Proteins, Olfactory Bulb, Corpus Striatum, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Neural Stem Cells, Tubulin, Lateral Ventricles, Animals, Eye Proteins, Promoter Regions, Genetic, Molecular Biology, Developmental Biology, Research Article, Protein Binding, Transcription Factors
Abstract

The striatum is a central regulator of behavior and motor function through the actions of D1 and D2 medium-sized spiny neurons (MSNs), which arise from a common lateral ganglionic eminence (LGE) progenitor. The molecular mechanisms of cell fate specification of these two neuronal subtypes are incompletely understood. Here, we found that deletion of murine Meis2, which is highly expressed in the LGE and derivatives, led to a large reduction in striatal MSNs due to a block in their differentiation. Meis2 directly binds to the Zfp503 and Six3 promoters and is required for their expression and specification of D1 and D2 MSNs, respectively. Finally, Meis2 expression is regulated by Dlx1/2 at least partially through the enhancer hs599 in the LGE subventricular zone. Overall, our findings define a pathway in the LGE whereby Dlx1/2 drives expression of Meis2, which subsequently promotes the fate determination of striatal D1 and D2 MSNs via Zfp503 and Six3.

Published
2022

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

Author

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, and Zhengang, Yang

Subjects
Homeodomain Proteins, Neurons, Receptors, Dopamine D2, Receptors, Dopamine D1, Gene Expression Regulation, Developmental, Mice, Transgenic, Nerve Tissue Proteins, DNA-Binding Proteins, Mice, nervous system, Neural Stem Cells, Animals, Eye Proteins, Transcription Factors, Research Article
Abstract

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.

Published
2018

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