The Physiological Characterization of Connexin41.8 and Connexin39.4, Which Are Involved in the Striped Pattern Formation of Zebrafish
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The zebrafish has a striped skin pattern on its body, and Connexin41.8 (Cx41.8) and Cx39.4 are involved in striped pattern formation. Mutations in these connexins change the striped pattern to a spot or labyrinth pattern. In this study, we characterized Cx41.8 and Cx39.4 after expression in Xenopus oocytes. In addition, we analyzed Cx41.8 mutants Cx41.8I203F and Cx41.8M7, which caused spot or labyrinth skin patterns, respectively, in transgenic zebrafish. In the electrophysiological analysis, the gap junctions formed by Cx41.8 and Cx39.4 showed distinct sensitivity to transjunctional voltage. Analysis of non-junctional (hemichannel) currents revealed a large voltage-dependent current in Cx39.4-expressing oocytes that was absent in cells expressing Cx41.8. Junctional currents induced by both Cx41.8 and Cx39.4 were reduced by co-expression of Cx41.8I203F and abolished by co-expression of Cx41.8M7. In the transgenic experiment, Cx41.8I203F partially rescued the Cx41.8 null mutant phenotype, whereas Cx41.8M7 failed to rescue the null mutant, and it elicited a more severe phenotype than the Cx41.8 null mutant, as evidenced by a smaller spot pattern. Our results provide evidence that gap junctions formed by Cx41.8 play an important role in stripe/spot patterning and suggest that mutations in Cx41.8 can effect patterning by way of reduced function (I203F) and dominant negative effects (M7). Our results suggest that functional differences in Cx41.8 and Cx39.4 relate to spot or labyrinth mutant phenotypes and also provide evidence that these two connexins interact in vivo and in vitro.
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Gja4 and Gja5b are gap junction proteins that are required autonomously by melanophores and xanthophores for homotypic and heterotypic interactions.
“Gja4 and Gja5b are gap junction proteins that are required autonomously by melanophores and xanthophores for homotypic and heterotypic interactions, i.e., interactions between the same or different pigment cell types, respectively15,16.”
From Genomic and genetic insights into speciation and pigment pattern diversification in <i>Danio</i> fishes (2025) · cites this paper as [16]
The Results (page unavailable) show that Cx41.8 and Cx39.4 are expressed in both melanophores and xanthophores, while the Discussion says they function together in interactions between those cell types. But the Results explicitly say GJA4 connexins were not analyzed, and the paper does not establish an autonomous requirement for either cell type or a role in interactions between pigment cells of the same type. Its ‘homotypic’ experiments concern connexin channels in oocytes, not same-type pigment-cell interactions. (LLM, conf=0.88)
Experimental — accuracy not yet measuredGap junctions containing Gja5b are critical for stripe patterning in D. rerio, with mutants developing spots similar to the wild-type pattern of D. tinwini.
“Gap junctions containing Gja5b are critical for stripe patterning in D. rerio with mutants developing spots similar to the wild-type pattern of D. tinwini15,16,54.”
From Genomic and genetic insights into speciation and pigment pattern diversification in <i>Danio</i> fishes (2025) · cites this paper as [16]
The Results and the ‘Connexins in Zebrafish Skin Patterning’ section report that Cx41.8 mutations change zebrafish stripes into spots, supporting the patterning claim. Our copy does not compare those spots with wild-type D. tinwini or explicitly identify Cx41.8 as Gja5b. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe common ancestor of Danio likely had horizontal stripes dependent on gap junctions between and amongst melanophores and xanthophores involving Gja4 and Gja5b as in D. rerio.
“Given that the common ancestor of Danio likely had horizontal stripes presumably dependent on gap junctions between and amongst melanophores and xanthophores involving Gja4 and Gja5b as in D. rerio15,16”
From Genomic and genetic insights into speciation and pigment pattern diversification in <i>Danio</i> fishes (2025) · cites this paper as [16]
The Discussion (page unavailable) supports a role for Cx41.8 and Cx39.4 in interactions between melanophores and xanthophores that create zebrafish stripes, and says transplantation experiments suggest gap junctions between the two cell types. It does not address whether the common ancestor of Danio had this pattern or establish junctions amongst cells of the same type. The Results (page unavailable) explicitly say GJA4 connexins were not analyzed, so the specific attribution to Gja4 and Gja5b is not established by this paper. (LLM, conf=0.88)
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Lu, J., Podobnik, M., Huang, J., McCluskey, B. M., McCarthy, S. A., Wood, J., Collins, J., Torrance, J., Sims, Y., Gao, D., et al. (2025) · doi:10.1101/2025.10.17.682988 · Cited by 4 · see citing works
- Authors
- Watanabe, M., Sawada, R., Aramaki, T., Skerrett, I. M., & Kondo, S.
- Affiliations
- The University of Osaka (JP)
- Buffalo State University (US)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Watanabe, Masakatsu
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 291
- Issue
- 3
- Pages
- 1053-1063
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4714190
- OpenAlex
- W2179190383
- Cited by
- 38
- References
- 1
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 6 · 2019: 7 · 2018: 2 · 2017: 2 · 2016: 2
- FWCI
- 0.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (26291049, 26650078, 25111714, 22127003)
- Core Research for Evolutional Science and Technology, Japan Science and Technology Agency
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
- Keywords
- gap junctions, transjunctional voltage, dominant negative effect, Xenopus oocyte expression, transgenic zebrafish
- MeSH terms
- Amino Acid Sequence, Animals, Female, Male, Molecular Sequence Data, Mutation, Oocytes, Phylogeny, Recombinant Proteins, Skin Pigmentation, Zebrafish, Sequence Alignment, Gene Deletion, Gap Junctions, Connexins, Gene Transfer Techniques, Patch-Clamp Techniques, Amino Acid Substitution, Zebrafish Proteins, Animals, Genetically Modified, Electrophysiological Phenomena, In Vitro Oocyte Maturation Techniques
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