Diversity of the cadherin-related neuronal receptor/protocadherin family and possible DNA rearrangement in the brain

Both the brain and the immune systems are complex. The complexity is generated by enormously diversified single cells. In the immune system, extensive cell death, gene regulation of immunoglobulin (Ig) and T-cell receptor (TCR) gene expression, and somatic rearrangement and mutations are known to generate an enormous diversity of lymphocytes. In this process, double-strand DNA breaks (DSBs) and DSB repair play significant roles. These processes at a DNA level are also physiologically significant in the nervous system during neurogenesis, and chromosomal variations have been detected in the nucleus of differentiated neurones. In another parallel with the immune system, cadherin-related neuronal receptors (CNRs) are diversified synaptic proteins. The CNR genes belong to protocadherin (Pcdh) gene clusters. Genomic organizations of CNR /Pcdh genes are similar to that of the Ig and TCR genes. Somatic mutations in and combinatorial gene regulation of CNR/Pcdh transcripts during neurogenesis have been reported. This review focuses on the diversity of the CNR/Pcdh genes and possible DNA diversification in the nervous system.