title: In vivo assembly of the axon initial segment in motor neurons.
abstract: The axon initial segment (AIS) is responsible for both the modulation of action potentials and the maintenance of neuronal polarity. Yet, the molecular mechanisms controlling its assembly are incompletely understood. Our study in single electroporated motor neurons in mouse embryos revealed that AnkyrinG (AnkG), the AIS master organizer, is undetectable in bipolar migrating motor neurons, but is already expressed at the beginning of axonogenesis at E9.5 and initially distributed homogeneously along the entire growing axon. Then, from E11.5, a stage when AnkG is already apposed to the membrane, as observed by electron microscopy, the protein progressively becomes restricted to the proximal axon. Analysis on the global motor neurons population indicated that Neurofascin follows an identical spatio-temporal distribution, whereas sodium channels and β4-spectrin only appear along AnkG(+) segments at E11.5. Early patch-clamp recordings of individual motor neurons indicated that at E12.5 these nascent AISs are already able to generate spikes. Using knock-out mice, we demonstrated that neither β4-spectrin nor Neurofascin control the distal-to-proximal restriction of AnkG.
authors.affiliation: INSERM, UMRS 952, 9 Quai St Bernard, 75005, Paris, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Le Bras
authors.forename: Amélie
authors.initials: A
authors.lastname: Fréal
authors.forename: Antonny
authors.initials: A
authors.lastname: Czarnecki
authors.forename: Pascal
authors.initials: P
authors.lastname: Legendre
authors.forename: Erika
authors.initials: E
authors.lastname: Bullier
authors.forename: Masayuki
authors.initials: M
authors.lastname: Komada
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Brophy
authors.forename: Marc
authors.initials: M
authors.lastname: Davenne
authors.forename: François
authors.initials: F
authors.lastname: Couraud
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D017487:Ankyrins / Q000378:metabolism*; D001369:Axons / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D013049:Spectrin / Q000378:metabolism*
chemical_list: C094681:Ank3 protein, mouse; D017487:Ankyrins; D015815:Cell Adhesion Molecules; D009414:Nerve Growth Factors; C504593:Nfasc protein, mouse; D013049:Spectrin