Analysis of Regional Cortical Development Genes

描述（由申请人提供）：多脑回畸形是一种人类大脑畸形疾病，其中大脑皮层组织受到干扰，导致形成过多的脑回。 GPR56（一种功能未知的G蛋白偶联受体）的突变导致额叶和顶叶的多微回症。 Gpr56在皮质祖细胞中表达，其产生成熟新皮质的几种细胞类型，表明Gpr56调节皮质祖细胞。 为了检验这一假设，通过在子宫内电穿孔野生型和突变的Gpr56等位基因和Gpr56 siRNA构建体，Gpr56将在胚胎新皮质中错误表达，并且分析电穿孔的皮质中皮质祖细胞的变化。 此外，Gpr56的鉴定表明新皮层发育所需的新信号通路。 为了确定Gpr56如何发挥信号传导作用，将鉴定Gpr56结合配偶体并测试其激活Gpr56的能力。 这些实验将有助于更好地理解新皮层发育和先天性神经系统疾病的原因。

DESCRIPTION (provided by applicant): Polymicrogyria is a human brain malformation disorder in which cerebral cortex organization is perturbed, causing the formation of too many gyri. Mutations in GPR56, a G protein-coupled receptor of unknown function, cause polymicrogyria of the frontal and parietal lobes. Gpr56 is expressed in cortical progenitors, which give rise to several cell-types of the mature neocortex, suggesting that Gpr56 regulates cortical progenitors. To test this hypothesis, Gpr56 will be misexpressed in embryonic neocortex by in utero electroporation of wild-type and mutated Gpr56 alleles and Gpr56 siRNA constructs, and electroporated cortex will be analyzed for changes in cortical progenitor cells. Furthermore, the identification of Gpr56 indicates a novel signaling pathway required for proper neocortex development. To determine how Gpr56 exerts is signaling effects, Gpr56 binding partners will be identified and tested for their ability to activate Gpr56. These experiments will contribute to a stronger understanding of neocortex development and the causes of congenital neurological disease.]