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Identification of immature cells in the adult mouse brain

成年小鼠大脑中未成熟细胞的鉴定

基本信息

批准号：
14380357
负责人：
KUWANO Ryozo
金额：
$ 9.66万
依托单位：
NIIGATA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

It is important to find molecules that express transiently in the early developmental stage to understand neuronal plasticity in the adult brain. We focused on a nerve growth cone involved in neurogenesis between the embryo and the early postnatal period. A membrane protein gmp46 (growth cone membrane protein with a molecular mass of 46 kDa) was isolated from the nerve growth cone-enriched fraction of newborn mouse brains. Gmp46 belongs to a member of the immunoglobulin super family and functions as an adhesion molecule. The gmp46 cDNA sequence was identical to the mouse homologue of the human coxsackievirus and adenovirus receptor (CAR). Gmp46/CAR, but not as the virus receptor, functions physiologically in neurogenesis events such as fasciculation of neuritis, axonal guidance, and recognition of the target cell as an adhesion molecule. By using a yeast two-hybrid screen to identify gmp46/CAR interacting protein via the PDZ domain at the C-terminal, we cloned PSD95 as a gmp46/CAR binding partner. The intracellular protein interactions appear to regulate a dynamic motility in neurogenesis. Western and northern blot analyses revealed that gmp46/CAR expressed predominantly in the nervous system and the highest level was observed in the newborn mouse brain followed by rapid decrease after birth. An abundant expression of gmp46/CAR was detected in the neuroepithelium of the neural tube in the embryos and the developing brain by immunohistochemical analysis. Then the expression of gmp46/CAR in these areas decreased and was barely detectable over postnatal 21 days. However, we found gmp46/CAR expression over 1 month in the dentate gyrus and the subventricular zone, where a few cells are proliferating. Based on our findings, we propose that gmp46/CAR transiently expresses in immature cells and plays a role on neuronetwork formations not only in embryo but also in adult brain.

找到在早期发育阶段短暂表达的分子对于了解成人大脑中的神经元可塑性非常重要。我们关注的是参与胚胎和产后早期神经发生的神经生长锥。从新生小鼠大脑的神经生长锥富集部分中分离出膜蛋白 gmp46（分子量为 46 kDa 的生长锥膜蛋白）。 Gmp46属于免疫球蛋白超家族的成员，具有粘附分子的功能。 gmp46 cDNA 序列与人类柯萨奇病毒和腺病毒受体 (CAR) 的小鼠同源物相同。 Gmp46/CAR，但不是作为病毒受体，在神经发生事件中发挥生理作用，例如神经炎的束颤、轴突引导和将靶细胞识别为粘附分子。通过使用酵母双杂交筛选，通过 C 端的 PDZ 结构域鉴定 gmp46/CAR 相互作用蛋白，我们将 PSD95 克隆为 gmp46/CAR 结合伴侣。细胞内蛋白质相互作用似乎调节神经发生中的动态运动。 Western和Northern印迹分析显示gmp46/CAR主要在神经系统中表达，在新生小鼠大脑中观察到最高水平，随后在出生后迅速下降。通过免疫组织化学分析，在胚胎神经管和发育中的大脑的神经上皮中检测到 gmp46/CAR 的丰富表达。然后这些区域的 gmp46/CAR 表达下降，在出生后 21 天几乎检测不到。然而，我们在齿状回和室下区发现 gmp46/CAR 表达超过 1 个月，其中一些细胞正在增殖。根据我们的发现，我们提出 gmp46/CAR 在未成熟细胞中瞬时表达，并且不仅在胚胎中而且在成人大脑中对神经网络形成发挥作用。