PUBLICATION
Voltage-gated sodium channel scn8a is required for innervation and regeneration of amputated adult zebrafish fins
- Authors
- Osorio-Méndez, D., Miller, A., Begeman, I.J., Kurth, A., Hagle, R., Rolph, D., Dickson, A.L., Chen, C.H., Halloran, M., Poss, K.D., Kang, J.
- ID
- ZDB-PUB-220723-8
- Date
- 2022
- Source
- Proceedings of the National Academy of Sciences of the United States of America 119: e2200342119 (Journal)
- Registered Authors
- Chen, Chen-Hui, Halloran, Mary, Kang, Junsu, Poss, Kenneth D.
- Keywords
- forward genetics, innervation, regeneration, scn8a, zebrafish
- MeSH Terms
-
- Animal Fins/physiology
- Animals
- Mammals/metabolism
- Regeneration/genetics
- Voltage-Gated Sodium Channels*
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 35867745 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Osorio-Méndez, D., Miller, A., Begeman, I.J., Kurth, A., Hagle, R., Rolph, D., Dickson, A.L., Chen, C.H., Halloran, M., Poss, K.D., Kang, J. (2022) Voltage-gated sodium channel scn8a is required for innervation and regeneration of amputated adult zebrafish fins. Proceedings of the National Academy of Sciences of the United States of America. 119:e2200342119.
Abstract
Teleost fishes and urodele amphibians can regenerate amputated appendages, whereas this ability is restricted to digit tips in adult mammals. One key component of appendage regeneration is reinnervation of the wound area. However, how innervation is regulated in injured appendages of adult vertebrates has seen limited research attention. From a forward genetics screen for temperature-sensitive defects in zebrafish fin regeneration, we identified a mutation that disrupted regeneration while also inducing paralysis at the restrictive temperature. Genetic mapping and complementation tests identify a mutation in the major neuronal voltage-gated sodium channel (VGSC) gene scn8ab. Conditional disruption of scn8ab impairs early regenerative events, including blastema formation, but does not affect morphogenesis of established regenerates. Whereas scn8ab mutations reduced neural activity as expected, they also disrupted axon regrowth and patterning in fin regenerates, resulting in hypoinnervation. Our findings indicate that the activity of VGSCs plays a proregenerative role by promoting innervation of appendage stumps.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping