PUBLICATION
Genetic deciphering of the antagonistic activities of the melanin-concentrating hormone and melanocortin pathways in skin pigmentation
- Authors
- Madelaine, R., Ngo, K.J., Skariah, G., Mourrain, P.
- ID
- ZDB-PUB-201212-23
- Date
- 2020
- Source
- PLoS Genetics 16: e1009244 (Journal)
- Registered Authors
- Madelaine, Romain, Mourrain, Philippe
- Keywords
- none
- MeSH Terms
-
- Animals
- Hypothalamic Hormones/genetics
- Hypothalamic Hormones/metabolism*
- Hypothalamus/cytology
- Hypothalamus/metabolism
- Melanins/genetics
- Melanins/metabolism*
- Melanocyte-Stimulating Hormones/genetics
- Melanocyte-Stimulating Hormones/metabolism
- Melanocytes/metabolism
- Neurons/metabolism
- Pituitary Hormones/genetics
- Pituitary Hormones/metabolism*
- Skin Pigmentation/genetics*
- Zebrafish
- PubMed
- 33301440 Full text @ PLoS Genet.
Citation
Madelaine, R., Ngo, K.J., Skariah, G., Mourrain, P. (2020) Genetic deciphering of the antagonistic activities of the melanin-concentrating hormone and melanocortin pathways in skin pigmentation. PLoS Genetics. 16:e1009244.
Abstract
The genetic origin of human skin pigmentation remains an open question in biology. Several skin disorders and diseases originate from mutations in conserved pigmentation genes, including albinism, vitiligo, and melanoma. Teleosts possess the capacity to modify their pigmentation to adapt to their environmental background to avoid predators. This background adaptation occurs through melanosome aggregation (white background) or dispersion (black background) in melanocytes. These mechanisms are largely regulated by melanin-concentrating hormone (MCH) and α-melanocyte-stimulating hormone (α-MSH), two hypothalamic neuropeptides also involved in mammalian skin pigmentation. Despite evidence that the exogenous application of MCH peptides induces melanosome aggregation, it is not known if the MCH system is physiologically responsible for background adaptation. In zebrafish, we identify that MCH neurons target the pituitary gland-blood vessel portal and that endogenous MCH peptide expression regulates melanin concentration for background adaptation. We demonstrate that this effect is mediated by MCH receptor 2 (Mchr2) but not Mchr1a/b. mchr2 knock-out fish cannot adapt to a white background, providing the first genetic demonstration that MCH signaling is physiologically required to control skin pigmentation. mchr2 phenotype can be rescued in adult fish by knocking-out pomc, the gene coding for the precursor of α-MSH, demonstrating the relevance of the antagonistic activity between MCH and α-MSH in the control of melanosome organization. Interestingly, MCH receptor is also expressed in human melanocytes, thus a similar antagonistic activity regulating skin pigmentation may be conserved during evolution, and the dysregulation of these pathways is significant to our understanding of human skin disorders and cancers.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping