PUBLICATION
longfin causes cis-ectopic expression of the kcnh2a ether-a-go-go K+ channel to autonomously prolong fin outgrowth
- Authors
- Stewart, S., Le Bleu, H.K., Yette, G.A., Henner, A.L., Robbins, A.E., Braunstein, J.A., Stankunas, K.
- ID
- ZDB-PUB-210602-7
- Date
- 2021
- Source
- Development (Cambridge, England) 148(11): (Journal)
- Registered Authors
- Stankunas, Kryn, Stewart, Scott
- Keywords
- Appendage development, Calcineurin, Fin regeneration, Ion signaling, Organ size, Zebrafish
- MeSH Terms
-
- Animal Fins/anatomy & histology
- Animal Fins/physiology*
- Animals
- CRISPR-Cas Systems
- Calcineurin/metabolism
- Cell Proliferation
- Ectopic Gene Expression/genetics
- Ectopic Gene Expression/physiology*
- Ether
- Ether-A-Go-Go Potassium Channels/genetics
- Ether-A-Go-Go Potassium Channels/metabolism*
- Gene Expression Regulation, Developmental
- Mesoderm/metabolism
- Organ Size
- Regeneration/physiology
- Signal Transduction/genetics
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 34061172 Full text @ Development
Citation
Stewart, S., Le Bleu, H.K., Yette, G.A., Henner, A.L., Robbins, A.E., Braunstein, J.A., Stankunas, K. (2021) longfin causes cis-ectopic expression of the kcnh2a ether-a-go-go K+ channel to autonomously prolong fin outgrowth. Development (Cambridge, England). 148(11):.
Abstract
Organs stop growing to achieve a characteristic size and shape in scale with the body of an animal. Likewise, regenerating organs sense injury extents to instruct appropriate replacement growth. Fish fins exemplify both phenomena through their tremendous diversity of form and remarkably robust regeneration. The classic zebrafish mutant longfint2 develops and regenerates dramatically elongated fins and underlying ray skeleton. We show longfint2 chromosome 2 overexpresses the ether-a-go-go-related voltage-gated potassium channel kcnh2a. Genetic disruption of kcnh2a in cis rescues longfint2, indicating longfint2 is a regulatory kcnh2a allele. We find longfint2 fin overgrowth originates from prolonged outgrowth periods by showing Kcnh2a chemical inhibition during late stage regeneration fully suppresses overgrowth. Cell transplantations demonstrate longfint2-ectopic kcnh2a acts tissue autonomously within the fin intra-ray mesenchymal lineage. Temporal inhibition of the Ca2+-dependent phosphatase calcineurin indicates it likewise entirely acts late in regeneration to attenuate fin outgrowth. Epistasis experiments suggest longfint2-expressed Kcnh2a inhibits calcineurin output to supersede growth cessation signals. We conclude ion signaling within the growth-determining mesenchyme lineage controls fin size by tuning outgrowth periods rather than altering positional information or cell-level growth potency.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping