The polymicrogyria-associated GPR56 promoter preferentially drives gene expression in developing GABAergic neurons in common marmosets.
The polymicrogyria-associated GPR56 promoter preferentially drives gene expression in developing GABAergic neurons in common marmosets.
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多微回相关GPR56启动子优先驱动普通绒猴发育中GABA能神经元的基因表达。
DOI：
10.1038/s41598-020-78608-4
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发表时间：
2020-12-09
影响因子：
4.6
通讯作者：
Okano H
中科院分区：
文献类型：
--
作者：
Murayama AY;Kuwako KI;Okahara J;Bae BI;Okuno M;Mashiko H;Shimogori T;Walsh CA;Sasaki E;Okano H
GPR56是黏附G蛋白偶联受体家族的成员，在发育中的大脑皮层细胞中大量表达，包括神经前体细胞和发育中的神经元。人类GPR56基因有多个假定的启动子，以不同的模式驱动GPR56蛋白的表达。与人类GPR56基因的编码突变可能导致GPR56功能障碍类似，GPR56非编码外显子1(E1m)上游的顺式调节元件15bp的纯合性缺失会导致大脑皮层畸形和癫痫。为了阐明e1m启动子驱动的GPR56在灵长类动物脑中的表达谱，我们建立了一个受人类最小e1m启动子控制表达绿色荧光蛋白的转基因绒猴株。与在大脑皮层脑室区高度丰富的内源性GPR56蛋白不同，EGFP主要在转基因胎儿大脑中发育中的神经元中表达。此外，EGFP主要在GABA能神经元中表达，而GPR56蛋白在GABA能和谷氨酸能神经元中均匀表达，这表明最小的e1m启动子对GABA能神经元具有优先活性。这些结果提示GPR56突变患者大脑皮层中的GABA能神经元可能起致病作用。
GPR56, a member of the adhesion G protein-coupled receptor family, is abundantly expressed in cells of the developing cerebral cortex, including neural progenitor cells and developing neurons. The human GPR56 gene has multiple presumptive promoters that drive the expression of the GPR56 protein in distinct patterns. Similar to coding mutations of the human GPR56 gene that may cause GPR56 dysfunction, a 15-bp homozygous deletion in the cis-regulatory element upstream of the noncoding exon 1 of GPR56 (e1m) leads to the cerebral cortex malformation and epilepsy. To clarify the expression profile of the e1m promoter-driven GPR56 in primate brain, we generated a transgenic marmoset line in which EGFP is expressed under the control of the human minimal e1m promoter. In contrast to the endogenous GPR56 protein, which is highly enriched in the ventricular zone of the cerebral cortex, EGFP is mostly expressed in developing neurons in the transgenic fetal brain. Furthermore, EGFP is predominantly expressed in GABAergic neurons, whereas the total GPR56 protein is evenly expressed in both GABAergic and glutamatergic neurons, suggesting the GABAergic neuron-preferential activity of the minimal e1m promoter. These results indicate a possible pathogenic role for GABAergic neuron in the cerebral cortex of patients with GPR56 mutations.
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SCN1A 5'基因组区的点突变降低启动子活性，与抗癫痫药物引起的轻度癫痫和癫痫发作加重有关
影响因子：
5.1
作者：
Gao, Qu-Wen;Hua, Li-Dong;Shi, Yi-Wu
通讯作者：
Shi, Yi-Wu
DOI：
10.1093/cercor/bhr301
发表时间：
2012-02
期刊：
Cerebral cortex (New York, N.Y. : 1991)
影响因子：
--
作者：
Kelava I;Reillo I;Murayama AY;Kalinka AT;Stenzel D;Tomancak P;Matsuzaki F;Lebrand C;Sasaki E;Schwamborn JC;Okano H;Huttner WB;Borrell V
通讯作者：
Borrell V
影响因子：
3.6
作者：
Higurashi N;Uchida T;Lossin C;Misumi Y;Okada Y;Akamatsu W;Imaizumi Y;Zhang B;Nabeshima K;Mori MX;Katsurabayashi S;Shirasaka Y;Okano H;Hirose S
通讯作者：
Hirose S
GPR56的进化动态替代剪接调节区域脑皮质模式。
DOI：
10.1126/science.1244392
发表时间：
2014-02-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bae BI;Tietjen I;Atabay KD;Evrony GD;Johnson MB;Asare E;Wang PP;Murayama AY;Im K;Lisgo SN;Overman L;Šestan N;Chang BS;Barkovich AJ;Grant PE;Topçu M;Politsky J;Okano H;Piao X;Walsh CA
通讯作者：
Walsh CA
影响因子：
16.2
作者：
Miller CT;Freiwald WA;Leopold DA;Mitchell JF;Silva AC;Wang X
通讯作者：
Wang X