title: The assembly of developing motor neurons depends on an interplay between spontaneous activity, type II cadherins and gap junctions.
abstract: A core structural and functional motif of the vertebrate central nervous system is discrete clusters of neurons or 'nuclei'. Yet the developmental mechanisms underlying this fundamental mode of organisation are largely unknown. We have previously shown that the assembly of motor neurons into nuclei depends on cadherin-mediated adhesion. Here, we demonstrate that the emergence of mature topography among motor nuclei involves a novel interplay between spontaneous activity, cadherin expression and gap junction communication. We report that nuclei display spontaneous calcium transients, and that changes in the activity patterns coincide with the course of nucleogenesis. We also find that these activity patterns are disrupted by manipulating cadherin or gap junction expression. Furthermore, inhibition of activity disrupts nucleogenesis, suggesting that activity feeds back to maintain integrity among motor neurons within a nucleus. Our study suggests that a network of interactions between cadherins, gap junctions and spontaneous activity governs neuron assembly, presaging circuit formation.
authors.affiliation: Wolfson Centre for Age-related Diseases, King's College London, Guy's Hospital Campus, London SE1 1UL, UK.
authors.forename: Karli
authors.initials: K
authors.lastname: Montague
authors.affiliation: Department of Developmental Neurobiology, King's College London, Guy's Hospital Campus, London SE1 1UL, UK.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Lowe
authors.affiliation: École de Neuroscience-Paris Île-de-France, ENP-DIM, 15 Rue de L'École de Médécine, Paris 75006, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Uzquiano
authors.affiliation: Department of Developmental Neurobiology, King's College London, Guy's Hospital Campus, London SE1 1UL, UK.
authors.forename: Athene
authors.initials: A
authors.lastname: Knüfer
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université de Bruxelles, Route de Lennik 808, Bruxelles B1070, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Astick
authors.affiliation: Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Price
authors.affiliation: Department of Developmental Neurobiology, King's College London, Guy's Hospital Campus, London SE1 1UL, UK s.guthrie@sussex.ac.uk.
authors.forename: Sarah
authors.identifier: 0000-0002-8446-9150
authors.initials: S
authors.lastname: Guthrie
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001933:Brain Stem / Q000196:embryology; D015820:Cadherins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002467:Cell Nucleus / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology*; D002642:Chick Embryo; D017629:Gap Junctions / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D051379:Mice; D009046:Motor Neurons / Q000166:cytology*; D041681:NIH 3T3 Cells
chemical_list: D015820:Cadherins; D002118:Calcium
keywords: Brainstem; Cadherins; Cell adhesion; Chick; Gap junctions; Motor neurons; Spontaneous activity