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Publication : Single-neuron diversity generated by Protocadherin-β cluster in mouse central and peripheral nervous systems.

First Author  Hirano K Year  2012
Journal  Front Mol Neurosci Volume  5
Pages  90 PubMed ID  22969705
Mgi Jnum  J:312046 Mgi Id  MGI:6782519
Doi  10.3389/fnmol.2012.00090 Citation  Hirano K, et al. (2012) Single-neuron diversity generated by Protocadherin-beta cluster in mouse central and peripheral nervous systems. Front Mol Neurosci 5:90
abstractText  The generation of complex neural circuits depends on the correct wiring of neurons with diverse individual characteristics. To understand the complexity of the nervous system, the molecular mechanisms for specifying the identity and diversity of individual neurons must be elucidated. The clustered protocadherins (Pcdh) in mammals consist of approximately 50 Pcdh genes (Pcdh-alpha, Pcdh-beta, and Pcdh-gamma) that encode cadherin-family cell surface adhesion proteins. Individual neurons express a random combination of Pcdh-alpha and Pcdh-gamma, whereas the expression patterns for the Pcdh-beta genes, 22 one-exon genes in mouse, are not fully understood. Here we show that the Pcdh-beta genes are expressed in a 3'-polyadenylated form in mouse brain. In situ hybridization using a pan-Pcdh-beta probe against a conserved Pcdh-beta sequence showed widespread labeling in the brain, with prominent signals in the olfactory bulb, hippocampus, and cerebellum. In situ hybridization with specific probes for individual Pcdh-beta genes showed their expression to be scattered in Purkinje cells from P10 to P150. The scattered expression patterns were confirmed by performing a newly developed single-cell 3'-RACE analysis of Purkinje cells, which clearly demonstrated that the Pcdh-beta genes are expressed monoallelically and combinatorially in individual Purkinje cells. Scattered expression patterns of individual Pcdh-beta genes were also observed in pyramidal neurons in the hippocampus and cerebral cortex, neurons in the trigeminal and dorsal root ganglion, GABAergic interneurons, and cholinergic neurons. Our results extend previous observations of diversity at the single-neuron level generated by Pcdh expression and suggest that the Pcdh-beta cluster genes contribute to specifying the identity and diversity of individual neurons.
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