Molecular regulation of myelin development and repair by Ick kinase

少突胶质细胞是髓鞘形成的大胶质细胞，见于大脑中央的所有区域。 神经系统。髓鞘的主要功能是确保快速和 电信号的忠实传输。在发育过程中，少突胶质细胞 前体细胞必须经过一系列的形态和分子生物学过程。 在它们完全分化为成熟髓鞘之前的变化 少突胶质细胞。少突胶质细胞的分化和髓鞘形成过程 是由蛋白质酪氨酸磷酸化调节的。最近我们发现Ick 胞浆丝氨酸/苏氨酸激酶在分化过程中选择性上调 OPC和Ick的破坏导致了OL分化的显著抑制。在……里面 在这一应用中，我们假设Ick促进OPC分化和轴突 Ick在发育过程中的髓鞘形成和增强随后的髓鞘修复 脱髓鞘侮辱。这个应用程序的第一个目标是检查Ick 在Ick条件突变小鼠中，髓鞘发育需要表达，并且 在OPC中诱导表达Ick蛋白促进小鼠发育髓鞘形成 可诱导的转基因小鼠。在第二个目标中，我们将检验Ick的假设 成年动物的轴突重新髓鞘形成也需要表达 诱导转基因小鼠过表达Ick可促进髓鞘恢复 脱髓鞘后 这一系列研究可以帮助我们理解 控制轴突髓鞘形成过程并提供对 小鼠少突胶质细胞再生和再髓鞘形成的分子机制 脱髓鞘疾病。

Oligodendrocytes are myelin-forming macroglia found in all regions of the central nervous system. The major function of myelin sheaths is to ensure the rapid and faithful transmission of electrical signals. During development, oligodendrocytes precursor cells (OPCs) have to go through a series of morphological and molecular changes before they become fully differentiated into mature myelinating oligodendrocytes. The differentiation and myelination processes of oligodendrocytes are regulated by protein tyrosine phosphorylation. Recently we found that Ick cytoplasmic serine/threonine kinase is selectively up-regulated in differentiating OPCs and disruption of Ick resulted a significant inhibition of OL differentiation. In this application, we hypothesize that Ick enhances OPC differentiation and axonal myelination by Ick during development and enhance myelin repair following demyelination insults. The first aim of this application is to examine whether Ick expression is required for myelin development in Ick conditional mutant mice, and induced expression of Ick protein in OPCs promotes developmental myelination in inducible transgenic mice. In the second aim, we will test the hypothesis that Ick expression is also required for axonal remyelination in adult animals and overexpression of Ick in inducible transgenic mice can promote myelin recovery following demyelination This line of study could help us understand molecular mechanisms that control axonal myelination process and provide insights into the development of molecular approaches to stimulate oligodendrocyte regeneration and remyelination in demyelinating diseases.