title: Brainstem respiratory oscillators develop independently of neuronal migration defects in the Wnt/PCP mouse mutant looptail.
abstract: The proper development and maturation of neuronal circuits require precise migration of component neurons from their birthplace (germinal zone) to their final positions. Little is known about the effects of aberrant neuronal position on the functioning of organized neuronal groups, especially in mammals. Here, we investigated the formation and properties of brainstem respiratory neurons in looptail (Lp) mutant mice in which facial motor neurons closely apposed to some respiratory neurons fail to migrate due to loss of function of the Wnt/Planar Cell Polarity (PCP) protein Vangl2. Using calcium imaging and immunostaining on embryonic hindbrain preparations, we found that respiratory neurons constituting the embryonic parafacial oscillator (e-pF) settled at the ventral surface of the medulla in Vangl2(Lp/+) and Vangl2(Lp/Lp) embryos despite the failure of tangential migration of its normally adjacent facial motor nucleus. Anatomically, the e-pF neurons were displaced medially in Lp/+ embryos and rostro-medially Lp/Lp embryos. Pharmacological treatments showed that the e-pF oscillator exhibited characteristic network properties in both Lp/+ and Lp/Lp embryos. Furthermore, using hindbrain slices, we found that the other respiratory oscillator, the preBötzinger complex, was also anatomically and functionally established in Lp mutants. Importantly, the displaced e-pF oscillator established functional connections with the preBötC oscillator in Lp/+ mutants. Our data highlight the robustness of the developmental processes that assemble the neuronal networks mediating an essential physiological function.
authors.affiliation: UPR 3294 Neurobiology and Development, CNRS Institute of Neurobiology A. Fessard, Gif-sur-Yvette, France. muriel.thoby-brisson@u-bordeaux2.fr
authors.forename: Muriel
authors.initials: M
authors.lastname: Thoby-Brisson
authors.forename: Julien
authors.initials: J
authors.lastname: Bouvier
authors.forename: Derrick M
authors.initials: DM
authors.lastname: Glasco
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Stewart
authors.forename: Charlotte
authors.initials: C
authors.lastname: Dean
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Murdoch
authors.forename: Jean
authors.initials: J
authors.lastname: Champagnat
authors.forename: Gilles
authors.initials: G
authors.lastname: Fortin
authors.forename: Anand
authors.initials: A
authors.lastname: Chandrasekhar
mesh_terms: D000818:Animals; D001683:Biological Clocks; D001933:Brain Stem / Q000473:pathology*; D002465:Cell Movement; D016764:Cell Polarity; D004622:Embryo, Mammalian / Q000473:pathology; D005145:Face; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D012119:Respiration; D012249:Rhombencephalon / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C109220:NBPhox protein; D014157:Transcription Factors; D051153:Wnt Proteins; C063843:insulin gene enhancer binding protein Isl-1