title: Distinct and Cooperative Functions for theProtocadherin-α, -β and -γ Clusters in Neuronal Survival and Axon Targeting.
abstract: The clusteredprotocadherin(Pcdh) genes are divided into thePcdhα, Pcdhβ, andPcdhγ clusters. Gene-disruption analyses in mice have revealed thein vivofunctions of thePcdhα andPcdhγ clusters. However, all Pcdh protein isoforms form combinatorialcis-hetero dimers and entertrans-homophilic interactions. Here we addressed distinct and cooperative functions in thePcdhclusters by generating six cluster-deletion mutants (Δα, Δβ, Δγ, Δαβ, Δβγ, and Δαβγ) and comparing their phenotypes: Δα, Δβ, and Δαβmutants were viable and fertile; Δγ mutants lived less than 12 h; and Δβγand Δαβγmutants died shortly after birth. ThePcdhα, Pcdhβ, andPcdhγ clusters were individually and cooperatively important in olfactory-axon targeting and spinal-cord neuron survival. Neurodegeneration was most severe in Δαβγmutants, indicating thatPcdhα andPcdhβ function cooperatively for neuronal survival. ThePcdhα, Pcdhβ, andPcdhγ clusters share roles in olfactory-axon targeting and neuronal survival, although to different degrees.
authors.affiliation: KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka UniversitySuita, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED)Suita, Japan.
authors.forename: Sonoko
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka UniversitySuita, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED)Suita, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kumagai
authors.affiliation: KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka UniversitySuita, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED)Suita, Japan.
authors.forename: Mitsue
authors.initials: M
authors.lastname: Hagihara
authors.affiliation: Division of Biomedical Science, Faculty of Medicine, University of Tsukuba Tsukuba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishimaru
authors.affiliation: KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University Suita, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Hirano
authors.affiliation: Bioresource Center, Graduate School of Medicine, Gunma University Maebashi, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kaneko
authors.affiliation: KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University Suita, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okayama
authors.affiliation: KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka UniversitySuita, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED)Suita, Japan.
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Hirayama
authors.affiliation: Section of Mammalian Transgenesis, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences Okazaki, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sanbo
authors.affiliation: AMED-CREST, Japan Agency for Medical Research and Development (AMED)Suita, Japan; Section of Mammalian Transgenesis, Center for Genetic Analysis of Behavior, National Institute for Physiological SciencesOkazaki, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Hirabayashi
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine Sapporo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka UniversitySuita, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED)Suita, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hirabayashi
authors.affiliation: KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka UniversitySuita, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED)Suita, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yagi
keywords: apoptosis; brainstem; cell adhesion molecule; gene targeting; locomotion; olfactory axon; protocadherin; spinal cord