A new genetic tool for analyzing protocadherin diversity in mice

描述(申请人提供)：大脑的功能依赖于具有数万亿突触连接的大约1000亿个神经元的精确组装。神经回路的发展涉及细胞间黏附、神经元间信号传递和细胞内大分子蛋白质复合体的组装等复杂的相互作用。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的存活和突触的发育。在这个项目中，我们将开发一个新的小鼠遗传模型来定义聚集性Pcdhs在电路发育中的重叠功能，独立于它们在神经元生存中的作用。这条调查路线 将促进我们对大脑神经回路精确度背后的分子多样性的理解。

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.