An ongoing role for Wnt signaling in differentiating melanocytes in vivo
Open accessAbstract
Summary: A role for Wnt signaling in melanocyte specification from neural crest is conserved across vertebrates, but possible ongoing roles in melanocyte differentiation have received little attention. Using a systems biology approach to investigate the gene regulatory network underlying stable melanocyte differentiation in zebrafish highlighted a requirement for a positive‐feedback loop involving the melanocyte master regulator Mitfa. Here, we test the hypothesis that Wnt signaling contributes to that positive feedback. We show firstly that Wnt signaling remains active in differentiating melanocytes and secondly that enhanced Wnt signaling drives elevated transcription of mitfa. We show that chemical activation of the Wnt signaling pathway at early stages of melanocyte development enhances melanocyte specification as expected, but importantly that at later (differentiation) stages, it results in altered melanocyte morphology, although melanisation is not obviously affected. Downregulation of Wnt signaling also results in altered melanocyte morphology and organization. We conclude that Wnt signaling plays a role in regulating ongoing aspects of melanocyte differentiation in zebrafish.
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Sox10, in conjunction with Wnt signalling, is required to activate and maintain mitfa transcription.
“In this lineage, Sox10, in conjunction with Wnt signalling, is required to activate and maintain mitfa transcription [13, 20, 24–26].”
From The MITF paralog tfec is required in neural crest development for fate specification of the iridophore lineage from a multipotent pigment cell progenitor (2021) · cites this paper as [26]
The Introduction says Sox10 and Wnt signaling act together to drive mitfa expression during melanocyte specification. The Results distinguish maintenance from that early activation: later Wnt input acts through a Sox10-independent, Mitfa-dependent positive-feedback loop. The source therefore does not support a continuing requirement for Sox10 in maintaining mitfa transcription. (LLM, conf=0.90)
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- Authors
- Vibert, L., Aquino, G., Gehring, I., Subkankulova, T., Schilling, T. F., Rocco, A., & Kelsh, R. N.
- Affiliations
- University of Bath (GB)
- University of Surrey (GB)
- University of California, Irvine (US)
- Corresponding author
- Kelsh, Robert N.
- Venue
- Pigment Cell & Melanoma Research
- Publisher
- Wiley
- Published
- 2017-03
- Volume
- 30
- Issue
- 2
- Pages
- 219-232
- ISSN
- 1755-1471 (ISSN-L)
- 1755-148X
- PMC
- PMC5360516
- OpenAlex
- W2562420363
- Cited by
- 35
- References
- 64
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 8 · 2019: 2 · 2018: 3 · 2017: 3
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Pigment Cell & Melanoma Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure (University of Bath) (publishedVersion, cc-by)
- Goldsmiths (University of London) (acceptedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- The University of Bath Online Publications Store (The University of Bath) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- HAL (submittedVersion, other-oa)
- Cambridge University Engineering Department Publications Database (submittedVersion)
- Apollo (cc-by)
- Funders
- University of Bath
- Biotechnology and Biological Sciences Research Council (BB/L00769X/1, BB/L007789/1)
- National Institutes of Health (R01 DE013828)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- Wnt signaling, melanocyte differentiation, neural crest, mitfa, positive feedback loop, gene regulatory networks, melanocyte morphology, melanization, zebrafish
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Embryo, Nonmammalian, Melanocytes, Zebrafish, Gene Expression Regulation, Developmental, Zebrafish Proteins, Gene Regulatory Networks, Wnt Signaling Pathway
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