title: Cell-autonomous axon growth of young motoneurons is triggered by a voltage-gated sodium channel.
abstract: Spontaneous electrical activity preceding synapse formation contributes to the precise regulation of neuronal development. Examining the origins of spontaneous activity revealed roles for neurotransmitters that depolarize neurons and activate ion channels. Recently, we identified a new molecular mechanism underlying fluctuations in spontaneous neuronal excitability. We found that embryonic motoneurons with a genetic loss of the low-threshold sodium channel NaV1.9 show fewer fluctuations in intracellular calcium in axonal compartments and growth cones than wild-type littermates. As a consequence, axon growth of NaV1.9-deficient motoneurons in cell culture is drastically reduced while dendritic growth and cell survival are not affected. Interestingly, NaV1.9 function is observed under conditions that would hardly allow a ligand- or neurotransmitter-dependent depolarization. Thus, NaV1.9 may serve as a cell-autonomous trigger for neuronal excitation. In this addendum, we discuss a model for the interplay between cell-autonomous local neuronal activity and local cytoskeleton dynamics in growth cone function.
authors.affiliation: Institute for Clinical Neurobiology, University of Würzburg, Würzburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wetzel
authors.forename: Sibylle
authors.initials: S
authors.lastname: Jablonka
authors.forename: Robert
authors.initials: R
authors.lastname: Blum
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism*; D009134:Muscular Atrophy, Spinal / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D062558:NAV1.9 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*
chemical_list: D062558:NAV1.9 Voltage-Gated Sodium Channel; C491885:Scn11a protein, mouse; D002118:Calcium