Molecular mechanism for generating and regenerating neuronal network by CNR family

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Brain is a complex system which is composed of enormous number of diverse neurons. CNR/Protocadherin (Pcdh) family is constituted with gene cluster like immunoglobulin and T cell receptor genes. The CNR/Pcdh proteins are localized in synapses and developmental axons. They are differentially expressed in individual neurons. In this project, to examine molecular mechanism for neural network formation and rearrangement, we focus to the CNR/Pcdh family in the brain. This project demonstrated that 1) mouse CNR1 (Pcdha4) protein gains cell adhesion activity via active integrin proteins, 2) we firstly revealed protein structure of protocadherin family by NMR spectroscopy, 3) CNR/Pcdha proteins highly express in the developmental axons and decline from initial formation of myelin, and their down regulation is regulated by myelination, 4) producing gene converted mice of the CNR/Pcdha family reveals their essential roles for precise neural network formation, and 5) we discover novel gene regulation of the CNR/Pcdh gene clusters in individual Purkinje cells. Thus this project successfully reveals that the diverse CNR/Pcdh family molecules play roles for cell adhesion activity, establishment for neuronal diversity and neural network formation in the brain.