scn1bb, a zebrafish ortholog of SCN1B expressed in excitable and nonexcitable cells, affects motor neuron axon morphology and touch sensitivity.
Voltage-gated Na(+) channels initiate and propagate action potentials in excitable cells. Mammalian Na(+) channels are composed of one pore-forming alpha-subunit and two beta-subunits. SCN1B encodes the Na(+) channel beta1-subunit that modulates channel gating and voltage dependence, regulates channel cell surface expression, and functions as a cell adhesion molecule (CAM). We recently identified scn1ba, a zebrafish ortholog of SCN1B. Here we report that zebrafish express a second beta1-like paralog, scn1bb. In contrast to the restricted expression of scn1ba mRNA in excitable cells, we detected scn1bb transcripts and protein in several ectodermal derivatives including neurons, glia, the lateral line, peripheral sensory structures, and tissues derived from other germ layers such as the pronephros. As expected for beta1-subunits, elimination of Scn1bb protein in vivo by morpholino knock-down reduced Na(+) current amplitudes in Rohon-Beard neurons of zebrafish embryos, consistent with effects observed in heterologous systems. Further, after Scn1bb knock-down, zebrafish embryos displayed defects in Rohon-Beard mediated touch sensitivity, demonstrating the significance of Scn1bb modulation of Na(+) current to organismal behavior. In addition to effects associated with Na(+) current modulation, Scn1bb knockdown produced phenotypes consistent with CAM functions. In particular, morpholino knock-down led to abnormal development of ventrally projecting spinal neuron axons, defasciculation of the olfactory nerve, and increased hair cell number in the inner ear. We propose that, in addition to modulation of electrical excitability, Scn1bb plays critical developmental roles by functioning as a CAM in the zebrafish embryonic nervous system.
Fein
Amanda J
AJ
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109-0632, USA.
Wright
Melissa A
MA
Slat
Emily A
EA
Ribera
Angeles B
AB
Isom
Lori L
LL
D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004847:Epithelial Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D007668:Kidney / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009046:Motor Neurons / Q000145:classification / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology*; D016415:Sequence Alignment / Q000379:methods; D015222:Sodium Channels / Q000276:immunology / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology; D014110:Touch / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism; D062547:Voltage-Gated Sodium Channel beta-1 Subunit; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015222:Sodium Channels; D014404:Tubulin; D062547:Voltage-Gated Sodium Channel beta-1 Subunit; D029961:Zebrafish Proteins; C523645:scn1ba protein, zebrafish; D049452:Green Fluorescent Proteins