Direct regulation of nacre , a zebrafish MITF homolog required for pigment cell formation, by the Wnt pathway
Open accessAbstract
We have shown that Wnt signals are necessary and sufficient for neural crest cells to adopt pigment cell fates. nacre , a zebrafish homolog of MITF , is required for pigment cell differentiation. We isolated a promoter region of nacre that contains Tcf/Lef binding sites, which can mediate Wnt responsiveness. This promoter binds to zebrafish Lef1 protein in vitro, and a nacre reporter construct is strongly repressed by dominant-negative Tcf in melanoma cells. Mutation of Tcf/Lef sites abolishes Lef1 binding and reporter function in vivo. Wnt signaling therefore directly activates nacre , which in turn leads to pigment cell differentiation.
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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 [24]
The Results (page not provided) support a role for Wnt signalling in activating nacre, the zebrafish MITF homolog: Tcf/Lef-site experiments support activation of nacre transcription in melanophore precursors. The cited paper does not establish that Sox10 acts in conjunction with Wnt or that the two are required to maintain transcription. (LLM, conf=0.88)
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MITF: master regulator of melanocyte development and melanoma oncogene
Levy, C., Khaled, M., & Fisher, D. E. (2006) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.07.008 · Cited by 1,169 · see citing works
Dorsky, R. I., Sheldahl, L. C., & Moon, R. T. (2002) · Developmental Biology · doi:10.1006/dbio.2001.0515 · Cited by 287 · see citing works
Self-citationMITF drives endolysosomal biogenesis and potentiates Wnt signaling in melanoma cells
Ploper, D., Taelman, V. F., Robert, L., Perez, B. S., Titz, B., Chen, H.-W., Graeber, T. G., von Euw, E., Ribas, A., & De Robertis, E. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1424576112 · Cited by 228 · see citing works
The roles of microphthalmia-associated transcription factor and pigmentation in melanoma
Hsiao, J. J., & Fisher, D. E. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.07.019 · Cited by 148 · see citing works
A sensitized mutagenesis screen identifies Gli3 as a modifier of Sox10 neurocristopathy
Matera, I., Watkins-Chow, D. E., Loftus, S. K., Hou, L., Incao, A., Silver, D. L., Rivas, C., Elliott, E. C., Baxter, L. L., & Pavan, W. J. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn110 · Cited by 60 · see citing works
Petratou, K., Spencer, S. A., Kelsh, R. N., & Lister, J. A. (2021) · PLOS ONE · doi:10.1371/journal.pone.0244794 · Cited by 55 · see citing works
- Authors
- Dorsky, R. I., Raible, D. W., & Moon, R. T.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2000-01-15
- Volume
- 14
- Issue
- 2
- Pages
- 158-162
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC316348
- OpenAlex
- W2107006976
- Cited by
- 279
- References
- 0
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 9 · 2023: 3 · 2022: 5 · 2021: 11 · 2020: 12 · 2019: 9 · 2018: 6 · 2017: 9 · 2016: 10 · 2015: 6 · 2014: 7 · 2013: 13 · 2012: 13
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- McKnight Foundation
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- nacre, Wnt signaling, TCF/LEF transcription factors, LEF1, neural crest cells, pigment cell differentiation, melanocytes, promoter regulation, zebrafish, melanoma cells
- MeSH terms
- Animals, Cell Division, DNA-Binding Proteins, Melanophores, Molecular Sequence Data, Pigmentation, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Sequence Homology, Nucleic Acid, Transcription Factors, Zebrafish, Signal Transduction, Gene Expression Regulation, Developmental, Zebrafish Proteins, Wnt Proteins, Microphthalmia-Associated Transcription Factor
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