PUBLICATION
Two different functions of Connexin43 confer two different bone phenotypes in zebrafish
- Authors
- Misu, A., Yamanaka, H., Aramaki, T., Kondo, S., Skerrett, I.M., Iovine, M.K., Watanabe, M.
- ID
- ZDB-PUB-160430-1
- Date
- 2016
- Source
- The Journal of biological chemistry 291(24): 12601-11 (Journal)
- Registered Authors
- Iovine, M. Kathryn, Kondo, Shigeru, Watanabe, Masakatsu
- Keywords
- bone, connexin, connexon (hemichannel), electrophysiology, gap junction, zebrafish
- MeSH Terms
-
- Animal Fins/growth & development
- Animal Fins/metabolism
- Animals
- Animals, Genetically Modified
- Blotting, Western
- Bone Development/genetics*
- Connexin 43/genetics*
- Connexin 43/physiology
- Female
- Larva/genetics
- Larva/growth & development
- Membrane Potentials/genetics
- Membrane Potentials/physiology
- Microscopy, Fluorescence
- Mutation*
- Oocytes/metabolism
- Oocytes/physiology
- Osteogenesis/genetics
- Patch-Clamp Techniques
- Phenotype
- Xenopus laevis
- Zebrafish/genetics*
- Zebrafish/growth & development
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/physiology
- PubMed
- 27129238 Full text @ J. Biol. Chem.
Citation
Misu, A., Yamanaka, H., Aramaki, T., Kondo, S., Skerrett, I.M., Iovine, M.K., Watanabe, M. (2016) Two different functions of Connexin43 confer two different bone phenotypes in zebrafish. The Journal of biological chemistry. 291(24):12601-11.
Abstract
Fish remain nearly the same shape as they grow, but there are two different modes of bone growth. Bones in the tail fin (fin ray segments) are added distally at the tips of the fins, and do not elongate once produced. On the other hand, vertebrae enlarge in proportion to body growth. To elucidate how bone growth is controlled, we investigated a zebrafish mutant, steopsel (stptl28d). Vertebrae of stptl28d/+ fish look normal in larvae (~30 day) but are distinctly shorter (59%-81%) than vertebrae of wild type fish in adults. In contrast, the lengths of fin rays are only slightly shorter (~95%) than those of the wild type in both larvae and adults. Positional cloning revealed that stp encodes Connexin43 (Cx43), a connexin that functions as a gap junction and hemichannel. Interestingly, cx43 was also identified as the gene causing the short-o-fin (sof) phenotype in which the fin ray segments are shorter but the vertebrae are normal. To identify the cause of this difference between the alleles, we expressed Cx43 exogenously in Xenopus oocytes and performed electrophysiological analysis of the mutant proteins. Gap junction coupling induced by Cx43stp or Cx43sof was reduced compared to Cx43-WT. On the other hand, only Cx43stp induced abnormally high (50 x wild type) transmembrane currents through hemichannels. Our results suggest that Cx43 plays critical and diverse roles in zebrafish bone growth.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping