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Cited by 31melanin and skin pigmentationDevelopmental Biology and Gene RegulationZebrafish Biomedical Research Applications

Endothelin receptor aa regulates proliferation and differentiation of Erb-dependent pigment progenitors in zebrafish

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Camargo-Sosa, Karen, Colanesi, Sarah, Müller, Jeanette, Schulte-Merker, Stefan, Stemple, Derek, Patton, E. Elizabeth, Kelsh, Robert N.·2019·PLOS Genetics
DOI 10.1371/journal.pgen.1007941PMC PMC6392274

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Abstract

Abstract Skin pigment patterns are important, being under strong selection for multiple roles including camouflage and UV protection. Pigment cells underlying these patterns form from adult pigment stem cells (APSCs). In zebrafish, APSCs derive from embryonic neural crest cells, but sit dormant until activated to produce pigment cells during metamorphosis. The APSCs are set-aside in an ErbB signaling dependent manner, but the mechanism maintaining quiescence until metamorphosis remains unknown. Mutants for a pigment pattern gene, parade , exhibit ectopic pigment cells localised to the ventral trunk. We show that parade encodes Endothelin receptor Aa, expressed in the blood vessels. Using chemical genetics, coupled with analysis of cell fate studies, we show that the ectopic pigment cells derive from APSCs. We propose that a novel population of APSCs exists in association with medial blood vessels, and that their quiescence is dependent upon Endothelin-dependent factors expressed by the blood vessels. Lay Abstract Pigment patterns are crucial for the many aspects of animal biology, for example, providing camouflage, enabling mate selection and protecting against UV irradiation. These patterns are generated by one or more pigment cell-types, localised in the skin, but derived from specialised stem cells (adult pigment stem cells, APSCs). In mammals, such as humans, but also in birds and fish, these APSCs derive from a transient population of multipotent progenitor cells, the neural crest. Formation of the adult pigment pattern is perhaps best studied in the zebrafish, where the adult pigment pattern is formed during a metamorphosis beginning around 21 days of development. The APSCs are set-aside in the embryo around 1 day of development, but then remain inactive until that metamorphosis, when they become activated to produce the adult pigment cells. We know something of how the cells are set-aside, but what signals maintain them in an inactive state is a mystery. Here we study a zebrafish mutant, called parade , which shows ectopic pigment cells in the embryo. We clone the parade gene, identifying it as ednraa encoding a component of a cell-cell communication process, which is expressed in blood vessels. By characterising the changes in the neural crest and in the pigment cells formed, and by combining this with an innovative assay identifying drugs that prevent the ectopic cells from forming, we deduce that the ectopic cells in the larva derive from precocious activation of APSCs to form pigment cells. We propose that a novel population of APSCs are associated with the blood vessels, that these are held in a quiescent state by signals coming from these vessels, and that these signals depend upon ednraa . Together this opens up an exciting opportunity to identify the signals maintaining APSC quiescence in zebrafish.

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  • Multipotent progenitors that give rise to adult melanophores, some xanthophores, and iridophores are established in the embryo and reside within peripheral nerves as development progresses.

    “Multipotent progenitors that give rise to adult melanophores, some xanthophores, and iridophores are established in the embryo and reside within peripheral nerves as development progresses (Budi et al., 2011; Budi et al., 2008; Camargo-Sosa et al., 2019; Dooley et al., 2013a; Singh et al., 2016).”

    From Thyroid hormone regulates distinct paths to maturation in pigment cell lineages (2019) · cites this paper as Camargo-Sosa et al., 2019

    The Introduction says adult pigment stem cells are set aside from neural crest cells during embryogenesis, with at least some occupying a niche within dorsal root ganglia. The Discussion says these cells produce adult melanophores and iridophores, with a small contribution to xanthophores. The claim overstates their location: the paper places at least some in ganglia and links others to the peripheral nervous system, but does not establish that the progenitors generally reside within peripheral nerves. (LLM, conf=0.84)

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Authors
Camargo-Sosa, K., Colanesi, S., Müller, J., Schulte-Merker, S., Stemple, D., Patton, E. E., & Kelsh, R. N.
Affiliations
  • University of Bath (GB)
  • Wellcome Trust (GB)
  • Western General Hospital (GB)
Corresponding author
Kelsh, Robert N.
ORCID
Venue
PLOS Genetics
Publisher
Public Library of Science (PLoS)
Published
2019-02-27
Volume
15
Issue
2
Pages
e1007941
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1007941
PMC
PMC6392274
OpenAlex
W2949553764
Cited by
31
References
2
Citations by year
2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 10 · 2020: 6 · 2019: 6
FWCI
3.15
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
Funders
  • Biotechnology and Biological Sciences Research Council (BB/L00769X/1)
  • Medical Research Council (MR/J001457/1, MC_PC_U127585840)
  • Consejo Nacional de Ciencia y Tecnología (329640/384511)
  • University of Bath
  • European Research Council (ZF-MEL-CHEMBIO-648489)
  • Melanoma Research Alliance (401181)
  • Wellcome Trust
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 › Cell Biology › Zebrafish Biomedical Research Applications
Keywords
ErbB signaling, neural crest cells, BMP signaling, melanocytes, iridophores, cell proliferation, quiescent cells, chemical genetic screen, zebrafish
MeSH terms
Animals, Cell Differentiation, Melanocytes, Melanophores, Models, Biological, Mutation, Neural Crest, Phenotype, Pigments, Biological, Skin Pigmentation, Zebrafish, Signal Transduction, Zebrafish Proteins, Receptor, Endothelin A, Cell Proliferation, Adult Stem Cells, ErbB Receptors

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