title: Allelic gene regulation of Pcdh-alpha and Pcdh-gamma clusters involving both monoallelic and biallelic expression in single Purkinje cells.
abstract: The molecular basis for providing the identity and diversity of single neurons is a key for realizing the brain system. Diverse protocadherin isoforms encoded by the Pcdh-alpha and Pcdh-gamma gene clusters are expressed in all of the vertebrates studied. For the Pcdh-alpha isoforms, differential expression patterns have been found in single Purkinje cells by unusual monoallelic and combinatorial types of gene regulation. Here we investigated total allelic gene regulation in the Pcdh-alpha and -gamma clusters, including the C-type variable exons (C1 to C5) and the Pcdh-gammaA and -gammaB variable exons in single Purkinje cells. Using split single-cell reverse transcription-PCR analysis, almost all of the Purkinje cells at postnatal day 21 biallelically expressed all the C-type isoforms, whereas the Pcdh-alpha isoforms showed both monoallelic and combinatorial expression. The Pcdh-gammaA and -gammaB isoforms also showed differential regulation in each cell with both monoallelic and combinatorial gene regulation. These data indicated that different types of allelic gene regulation (monoallelic versus biallelic) occurred in the Pcdh-alpha and -gamma clusters, although they were spliced into the same constant exons. It has been reported that each C-type Pcdh-alpha or -gamma transcript has a different expression pattern during brain development, suggesting that the different C-type variable exons may code temporal diversity, although the Pcdh-alpha, -gammaA, and -gammaB isoforms were differential and combinatorial gene regulation within a single cell. Thus, the multiple gene regulations in the Pcdh-alpha and -gamma clusters had a potential mechanism for increasing the diversity of individual neurons in the brain.
authors.affiliation: KOKORO Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kaneko
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Esumi
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Hirayama
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hirabayashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yagi
mesh_terms: D000483:Alleles; D000818:Animals; D001921:Brain / Q000196:embryology; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics*; D005091:Exons; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D005810:Multigene Family; D009474:Neurons / Q000378:metabolism; D020033:Protein Isoforms; D011689:Purkinje Cells
chemical_list: D000070585:Cadherin Related Proteins; D015820:Cadherins; C464785:Gamma-protocadherins; D020033:Protein Isoforms