How Fishes Color their Skin: Genetic Analysis of Melanocortin Receptor 2 (MC2R) in Fish Pigmentation.
Supervisor: Josep Rotllant (CSIC)
The melanocortin system is involved in numerous physiological processes in vertebrates such as pigmentation, steroidogenesis and feeding behavior. Here we are showing, the melanin based pigmentation, and high stress-induced cortisol are correlated and linked with melanocortin receptor’s signaling. In Fishes, Mc1r functionality is well studied, a key melanocortin receptor involve in establishing a highly conserved dorsal ventral pigmentation pattern. However, the possible role of the other melanocortin receptors in pigmentation is yet to be explored. The main objective of this work was to characterize the functional role of Mc2r (mainly responsible for cortisol secretion) in the formation of the pigmentation pattern in zebrafish (Danio rerio). In humans, it is well known that MC2R is expressed in the adrenal gland and controls steroidogenesis. Absence of MC2R, excess of ACTH interacts with other Melanocortin receptors and causes hyperpigmentation. Thus, using CRISPR/cas9 genetic tool, mc2r homozygous knockout (mc2rKO) was created and their pigmentary phenotype and genotype was characterized. Loss of function of mc2r resulted in low glucocorticoid and hyperpigmentation in mutant fishes which is characterized by a reduction in countershading and a general increase in the number of xanthophores/melanophores. We also related our results to demonstrate the hypothesis of Acth ligands to other Mcrs and controls the cortisol level.

Key words: Pigmentation, Mc2r, Cortisol, Steroidogenesis, Mc1r, Acth, CRISPR-Cas9, melanophores, xanthophores, zebrafish.