title: Two Different Functions of Connexin43 Confer Two Different Bone Phenotypes in Zebrafish.
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 (stp(tl28d)). Vertebrae of stp(tl28d) (/+) fish look normal in larvae (∼30 days) 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-of-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 Cx43(stp) or Cx43(sof) was reduced compared with Cx43-WT. On the other hand, only Cx43(stp) induced abnormally high (50× wild type) transmembrane currents through hemichannels. Our results suggest that Cx43 plays critical and diverse roles in zebrafish bone growth.
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Misu
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamanaka
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Aramaki
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan; CREST, Japan Science and Technology Agency, 1-3 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kondo
authors.affiliation: Biology Department, Buffalo State College, Buffalo, New York 14222.
authors.forename: I Martha
authors.initials: IM
authors.lastname: Skerrett
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania 18015.
authors.forename: M Kathryn
authors.initials: MK
authors.lastname: Iovine
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: watanabe-m@fbs.osaka-u.ac.jp.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D058500:Animal Fins / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D001846:Bone Development / Q000235:genetics*; D018031:Connexin 43 / Q000235:genetics* / Q000502:physiology; D005260:Female; D007814:Larva / Q000235:genetics / Q000254:growth & development; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology; D008856:Microscopy, Fluorescence; D009154:Mutation; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics; D018408:Patch-Clamp Techniques; D010641:Phenotype; D014982:Xenopus laevis; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology
chemical_list: D018031:Connexin 43; D029961:Zebrafish Proteins
keywords: bone; connexin; connexon (hemichannel); electrophysiology; gap junction; zebrafish