A new genetic tool for analyzing protocadherin diversity in mice

描述（由申请人提供）：大脑的功能依赖于大约1000亿个神经元与数万亿个突触连接的精确组装。神经回路的发展涉及细胞间粘附、神经元间信号传导和细胞内大分子蛋白质复合物的组装的复杂相互作用。三个串联排列的原钙粘蛋白（Pcdh）基因簇，即Pcdh-<$、Pcdh-<$和Pcdh-？，通过不同的机制调节神经元存活和突触发育。在这个项目中，我们将开发一个新的小鼠遗传模型，以确定重叠功能的集群Pcdhs在电路的发展，独立于他们的作用，在神经元的生存。这条调查线 将促进我们对大脑神经回路精确性背后的分子多样性的理解。 公共卫生相关性：哺乳动物神经回路精确性和复杂性的分子基础在很大程度上仍然不确定。本项目的目标是产生一种新的遗传工具，用于分析大脑中细胞表面分子-原钙粘蛋白大家族的功能。

DESCRIPTION (provided by applicant): The function of the brain relies on the precise assembly of approximately 100 billion neurons with trillions of synaptic connections. The development of neural circuitry involves a complex interplay of cell-cell adhesion, inter-neuronal signaling and assembly of intracellular macromolecular protein complexes. The three tandem-arrayed protocadherin (Pcdh) gene clusters, namely Pcdh-¿, Pcdh-¿ and Pcdh-?, regulate neuronal survival and synaptic development by distinct mechanisms. In this project, we will develop a new mouse genetic model to define the overlapping function of clustered Pcdhs in circuit development, independently from their role in neuronal survival. This line of investigation will advance our understanding of molecular diversity underlying the precision of neural circuitry in the brain. PUBLIC HEALTH RELEVANCE: Molecular basis underlying the precision and complexity of mammalian neural circuits remains largely undefined. The objective of this project is to generate a new genetic tool for analyzing the function of a large family of cell surface molecules-protocadherins in the brain.