title: Gamma protocadherins are required for survival of spinal interneurons.
abstract: The murine genome contains approximately 70 protocadherin (Pcdh) genes. Many are expressed in the nervous system, suggesting that Pcdhs may specify neuronal connectivity. Here, we analyze the 22 contiguous genes of the Pcdh-gamma cluster. Individual neurons express subsets of Pcdh-gamma genes. Pcdh-gamma proteins are present in most neurons and associated with, but not confined to, synapses. Early steps in neuronal migration, axon outgrowth, and synapse formation proceed in mutant mice lacking all 22 Pcdh-gamma genes. At late embryonic stages, however, dramatic neurodegeneration leads to neonatal death. In mutant spinal cord, many interneurons are lost, but sensory and motor neurons are relatively spared. In cultures from mutant spinal cord, neurons differentiate and form synapses but then die. Thus, Pcdh-gamma genes are dispensable for at least some aspects of connectivity but required for survival of specific neuronal types.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Wang
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Weiner
authors.forename: Sabine
authors.initials: S
authors.lastname: Levi
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Craig
authors.forename: Allan
authors.initials: A
authors.lastname: Bradley
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sanes
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000502:physiology; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002458:Cell Fractionation; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D013569:Synapses / Q000737:chemistry / Q000378:metabolism
chemical_list: D000070585:Cadherin Related Proteins; D015820:Cadherins; C464785:Gamma-protocadherins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins