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首页> 外文期刊>Molecular and Cellular Biology >Regulation of the Protocadherin Celsr3 Gene and Its Role in Globus Pallidus Development and Connectivity
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Regulation of the Protocadherin Celsr3 Gene and Its Role in Globus Pallidus Development and Connectivity

机译：钙粘蛋白原Celsr3基因的调节及其在Globus Pallidus发育和连接中的作用

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The globus pallidus (GP) is a central component of basal ganglia whose malfunctions cause a variety of neuropsychiatric disorders as well as cognitive impairments in neurodegenerative diseases such as Parkinson's disease. Here we report that the protocadherin gene Celsr3 is regulated by the insulator CCCTC-binding factor (CTCF) and the repressor neuron-restrictive silencer factor (NRSF, also known as REST) and is required for the development and connectivity of GP. Specifically, CTCF/cohesin and NRSF inhibit the expression of Celsr3 through specific binding to its promoter. In addition, we found that the Celsr3 promoter interacts with CTCF/cohesin-occupied neighboring promoters. In Celsr3 knockout mice, we found that the ventral GP is occupied by aberrant calbindin-positive cholinergic neurons ectopic from the nucleus basalis of Meynert. Furthermore, the guidepost cells for thalamocortical axonal development are missing in the caudal GP. Finally, axonal connections of GP with striatum, subthalamic nucleus, substantia nigra, and raphe are compromised. These data reveal the essential role of Celsr3 in GP development in the basal forebrain and shed light on the mechanisms of the axonal defects caused by the Celsr3 deletion.
机译：苍白球（GP）是基底神经节的重要组成部分，其功能异常会导致多种神经精神疾病以及帕金森氏病等神经退行性疾病的认知障碍。在这里，我们报道原钙粘蛋白基因 Celsr3 受绝缘子CCCTC结合因子（CTCF）和阻遏神经元限制性沉默子因子（NRSF，也称为REST）调控，是发育和发育所必需的。 GP的连通性。具体而言，CTCF / cohesin和NRSF通过与启动子特异性结合来抑制 Celsr3 的表达。另外，我们发现 Celsr3 启动子与CTCF /粘着蛋白占据的邻近启动子相互作用。在 Celsr3 敲除小鼠中，我们发现腹侧GP被Meynert核基底异位的异常钙化蛋白阳性胆碱能神经元占据。此外，尾部GP中缺少用于丘脑皮层轴突发育的路标细胞。最后，GP与纹状体，丘脑下核，黑质和缝隙的轴突连接受到损害。这些数据揭示了 Celsr3 在基底前脑的GP发育中的重要作用，并阐明了 Celsr3 缺失引起的轴突缺损的机制。

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