RRC ID 2454
Author Pineda RH, Svoboda KR, Wright MA, Taylor AD, Novak AE, Gamse JT, Eisen JS, Ribera AB.
Title Knockdown of Nav1.6a Na+ channels affects zebrafish motoneuron development.
Journal Development
Abstract In addition to rapid signaling, electrical activity provides important cues to developing neurons. Electrical activity relies on the function of several different types of voltage-gated ion channels. Whereas voltage-gated Ca2+ channel activity regulates several aspects of neuronal differentiation, much less is known about developmental roles of voltage-gated Na+ channels, essential mediators of electrical signaling. Here, we focus on the zebrafish Na+ channel isotype, Nav1.6a, which is encoded by the scn8a gene. A restricted set of spinal neurons, including dorsal sensory Rohon-Beard cells, two motoneuron subtypes with different axonal trajectories, express scn8a during embryonic development. CaP, an early born primary motoneuron subtype with ventrally projecting axons expresses scn8a, as does a class of secondary motoneurons with axons that project dorsally. To test for developmental roles of scn8a, we knocked down Nav1.6a protein using antisense morpholinos. Na+ channel protein and current amplitudes were reduced in neurons that express scn8a. Furthermore, Nav1.6a knockdown altered axonal morphologies of some but not all motoneurons. Dorsally projecting secondary motoneurons express scn8a and displayed delayed axonal outgrowth. By contrast, CaP axons developed normally, despite expression of the gene. Surprisingly, ventrally projecting secondary motoneurons, a population in which scn8a was not detected, displayed aberrant axonal morphologies. Mosaic analysis indicated that effects on ventrally projecting secondary motoneurons were non cell-autonomous. Thus, voltage-gated Na+ channels play cell-autonomous and non cell-autonomous roles during neuronal development.
Volume 133(19)
Pages 3827-36
Published 2006-10-1
DOI 10.1242/dev.02559
PII dev.02559
PMID 16943272
MeSH Animals Axons / chemistry Axons / metabolism Axons / ultrastructure* Cell Survival Embryo, Nonmammalian / drug effects Embryo, Nonmammalian / metabolism Embryonic Development / drug effects Embryonic Development / genetics Motor Neurons / chemistry Motor Neurons / cytology* Motor Neurons / metabolism NAV1.6 Voltage-Gated Sodium Channel Oligonucleotides, Antisense / pharmacology RNA, Messenger / analysis RNA, Messenger / metabolism Sodium Channels / genetics Sodium Channels / metabolism Spinal Cord / cytology Spinal Cord / embryology* Spinal Cord / metabolism Zebrafish / embryology* Zebrafish / genetics Zebrafish Proteins / antagonists & inhibitors* Zebrafish Proteins / genetics Zebrafish Proteins / metabolism
IF 5.611
Times Cited 52
Zebrafish rw0