Abstract
The Chinese tongue sole (Cynoglossus semilaevis) is a flatfish with distinctive asymmetry in its body coloration. The melanism (hyperpigmentation) in both the blind side and ocular side of C. semilaevis gives it an extremely low commercial value. However, the fundamental molecular mechanism of this melanism remains unclear. Melanocortin 1 receptor (MC1R), a GTP-binding protein-coupled receptor, is considered to play a vital role in the physiology of the vertebrate pigment system. In order to confirm the contribution of MC1R to the body coloration of C. semilaevis, the expression levels of Mc1r mRNA were measured in seven tissue types at different developmental stages of normal and melanistic C. semilaevis. The expression levels of Mc1r mRNA in the heart, brain, liver, kidney, ocular-side skin, and blind-side skin of melanistic C. semilaevis were significantly higher than that of normal C. semilaevis in all developmental stages. Moreover, the knocking down of Mc1r in the C. semilaevis liver cell line (HTLC) increased the expression of the downstream genes microphthalmia transcription factor (Mitf) and tyrosinase-related protein 1 (Tyrp1) in the pigmentation pathway. Thus, the present data suggest that MC1R might play important roles in Tyrp1- and Mitf-mediated pigment synthesis in C. semilaevis.
Similar content being viewed by others
References
Bagnara JT (1998) Comparative anatomy and physiology of pigment cells in nonmammalian tissues. In: Nordland J, Boissy R, Hearing V, King R, Ortonne J (eds) The Pigmentary system. Physiology and Pathophysiology Oxford University Press, New York, pp 9–40
Bharti K, Gasper M, Ou J, Brucato M, Clore-Gronenborn K, Pickel J, Arnheiter H (2012) A regulatory loop involving PAX6, MITF, and WNT signaling controls retinal pigment epithelium development. PLoS Genet 8:e1002757
Boglino A, Wishkerman A, Darias MJ, Andree KB, de la Iglesia P, Estevez A, Gisbert E (2013) High dietary arachidonic acid levels affect the process of eye migration and head shape in pseudoalbino Senegalese sole Solea senegalensis early juveniles. J Fish Biol 83:1302–1320
Cal L, Suarez-Bregua P, Cerda-Reverter JM, Braasch I, Rotllant J (2017) Fish pigmentation and the melanocortin system. Comp Biochem Physiol A Mol Integr Physiol 211:26–33
Chida D, Nakagawa S, Nagai S, Sagara H, Katsumata H, Imaki T, Suzuki H, Mitani F, Ogishima T, Shimizu C, Kotaki H, Kakuta S, Sudo K, Koike T, Kubo M, Iwakura Y (2007) Melanocortin 2 receptor is required for adrenal gland development, steroidogenesis, and neonatal gluconeogenesis. Proc Natl Acad Sci U S A 104:18205–18210
Cone RD (2006) Studies on the physiological functions of the melanocortin system. Endocr Rev 27:736–749
Cone RD, Lu D, Koppula S, Vage DI, Klungland H, Boston B, Chen W, Orth DN, Pouton C, Kesterson RA (1996) The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation. Recent Prog Horm Res 51:287–317
Corso J, Goncalves GL, de Freitas TR (2012) Sequence variation in the melanocortin-1 receptor (MC1R) pigmentation gene and its role in the cryptic coloration of two South American sand lizards. Genet Mol Biol 35:81–87
Cronin JC, Wunderlich J, Loftus SK, Prickett TD, Wei X, Ridd K, Vemula S, Burrell AS, Agrawal NS, Lin JC, Banister CE, Buckhaults P, Rosenberg SA, Bastian BC, Pavan WJ, Samuels Y (2009) Frequent mutations in the MITF pathway in melanoma. Pigment Cell Melanoma Res 22:435–444
D'Orazio JA, Nobuhisa T, Cui R, Arya M, Spry M, Wakamatsu K, Igras V, Kunisada T, Granter SR, Nishimura EK, Ito S, Fisher DE (2006) Topical drug rescue strategy and skin protection based on the role of Mc1r in UV-induced tanning. Nature 443:340–344
Dorsky RI, Raible DW, Moon RT (2000) Direct regulation of nacre, a zebrafish MITF homolog required for pigment cell formation, by the Wnt pathway. Genes Dev 14:158–162
Estévez A, Kanazawa A (1995) Effect of (n–3) PUFA and vitamin A Artemia enrichment on pigmentation success of turbot, Scophthalmus maximus (L). Aquacult. Nutr 1:159–168
Estévez A, McEvoy LA, Bell JG, Sargent JR (1999) Growth, survival, lipid composition and pigmentation of turbot (Scophthalmus maximus) larvae fed live prey enriched in arachidonic and eicosapentaenoic acids. Aquaculture 180:321–343
Fujii R (1993) Coloration and chromatophores. In: Evans D (ed) The physiology of fishes. FL CRC Press, Boca Raton, pp 535–562
Garcia-Borron JC, Sanchez-Laorden BL, Jimenez-Cervantes C (2005) Melanocortin-1 receptor structure and functional regulation. Pigment Cell Res 18:393–410
Gantz I, Shimoto Y, Konda Y, Miwa H, Dickinson CJ, Yamada T (1994) Molecular cloning, expression, and characterization of a fifth melanocortin receptor. Biochem Biophys Res Commun 200(3):1214–1220
Gross JB, Borowsky R, Tabin CJ (2009) A novel role for Mc1r in the parallel evolution of depigmentation in independent populations of the cavefish Astyanax mexicanus. PLoS Genet 5:e1000326
Haga Y, Suzuki T, Kagechika H, Takeuchi T (2003) Retinoic acid receptor-selective agonist causes jaw deformity in the Japanese flounder. Aquaculture 221:381–392
Hamre K, Holen E, Moren M (2007) Pigmentation and eye migration in Atlantic halibut (Hippoglossus hippoglossus L.) larvae: new findings and hypotheses. Aquac Nutr 13(1):65–80
Han J, Hong WS, Wang Q, Zhang TT, Chen SX (2019) The regulation of melanocyte-stimulating hormone on the pigment granule dispersion in the xanthophores and melanophores of the large yellow croaker (Larimichthys crocea). Aquaculture 507:7–20
Higdon CW, Mitra RD, Johnson SL (2013) Gene expression analysis of zebrafish melanocytes, iridophores, and retinal pigmented epithelium reveals indicators of biological function and developmental origin. PLoS One 8:e67801
Iwata N, Kikuchi K (1998) Effects of sandy substrate and light on hypermelanosis of the blind side in cultured Japanese flounder Paralichthys olivaceus. Environm Biol Fisher 52:291–297
Jackson IJ (1997) Homologous pigmentation mutations in human, mouse and other model organisms. Hum Mol Genet 6:1613–1624
Ji LQ, Rao YZ, Zhang Y, Chen R, Tao YX (2020) Regulation of melanocortin-1 receptor pharmacology by melanocortin receptor accessory protein 2 in orange-spotted grouper (Epinephelus coioides). Gen Comp Endocrinol 285:113291
Klovins J, Haitina T, Fridmanis D, Kilianova Z, Kapa I, Fredriksson R, Gallo-Payet N, Schioth HB (2004) The melanocortin system in Fugu: determination of POMC/AGRP/MCR gene repertoire and synteny, as well as pharmacology and anatomical distribution of the MCRs. Mol Biol Evol 21:563–579
Kobayashi Y, Chiba H, Mizusawa K, Suzuki N, Cerda-Reverter JM, Takahashi A (2011) Pigment-dispersing activities and cortisol-releasing activities of melanocortins and their receptors in xanthophores and head kidneys of the goldfish Carassius auratus. Gen Comp Endocrinol 173:438–446
Koga A, Hori H (1999) Homogeneity in the structure of the medaka fish transposable element Tol2. Genet Res 73:7–14
Konieczkowski DJ, Johannessen CM, Abudayyeh O, Kim JW, Cooper ZA, Piris A, Frederick DT, Barzily-Rokni M, Straussman R, Haq R, Fisher DE, Mesirov JP, Hahn WC, Flaherty KT, Wargo JA, Tamayo P, Garraway LA (2014) A melanoma cell state distinction influences sensitivity to MAPK pathway inhibitors. Cancer Discov 4:816–827
Kottler VA, Kunstner A, Schartl M (2015) Pheomelanin in fish? Pigment Cell Melanoma Res 28:355–356
Li Z, Yang L, Wang J, Shi W, Pawar RA, Liu Y (2010) β-Actin is a useful internal control for tissue-specific gene expression studies using quantitative real-time PCR in the half-smooth tongue sole Cynoglossus semilaevis challenged with LPS or Vibrio anguillarum. Fish Shellfish Immunol 29(1):89–93
Lin JY, Fisher DE (2007) Melanocyte biology and skin pigmentation. Nature 445:843–850
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408
Lund I, Steenfeldt SJ, Hansen BW (2007) Effect of dietary arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid on survival, growth and pigmentation in larvae of common sole (Solea solea L.). Aquaculture 273:532–544
Luttrell LM, Lefkowitz RJ (2002) The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals. J Cell Sci 115:455–465
Matsuda N, Kasagi S, Nakamaru T, Masuda R, Takahashi A, Tagawa M (2018) Left-right pigmentation pattern of Japanese flounder corresponds to expression levels of melanocortin receptors (MC1R and MC5R), but not to agouti signaling protein 1 (ASIP1) expression. Gen Comp Endocrinol 262:90–98
Mountjoy KG, Robbins LS, Mortrud MT, Cone RD (1992) The cloning of a family of genes that encode the melanocortin receptors. Science 257:1248–1251
Pointer MA, Mundy NI (2008) Testing whether macroevolution follows microevolution: are colour differences among swans (Cygnus) attributable to variation at the MCIR locus? BMC Evol Biol 8:249
Roberts DW, Newton RA, Leonard JH, Sturm RA (2008) Melanocytes expressing MC1R polymorphisms associated with red hair color have altered MSH-ligand activated pigmentary responses in coculture with keratinocytes. J Cell Physiol 215:344–355
Robertson HM, Thomas JH (2006) The putative chemoreceptor families of C. elegans. In: WormBook, pp 1–12
Rodrigues AR, Sousa D, Almeida H, Gouveia AM (2017) Cell surface targeting of the melanocortin 5 receptor (MC5R) requires serine-rich terminal motifs. Biochim Biophys Acta Mol Cell Res 1864:1217–1226
Sanchez E, Rubio VC, Cerda-Reverter JM (2010) Molecular and pharmacological characterization of the melanocortin type 1 receptor in the sea bass. Gen Comp Endocrinol 165:163–169
Selz Y, Braasch I, Hoffmann C, Schmidt C, Schultheis C, Schartl M, Volff JN (2007) Evolution of melanocortin receptors in teleost fish: the melanocortin type 1 receptor. Gene 401:114–122
Shao C, Bao B, Xie Z, Chen X, Li B, Jia X, Yao Q, Orti G, Li W, Li X, Hamre K, Xu J, Wang L, Chen F, Tian Y, Schreiber AM, Wang N, Wei F, Zhang J, Dong Z, Gao L, Gai J, Sakamoto T, Mo S, Chen W, Shi Q, Li H, Xiu Y, Li Y, Xu W, Shi Z, Zhang G, Power DM, Wang Q, Schartl M, Chen S (2017) The genome and transcriptome of Japanese flounder provide insights into flatfish asymmetry. Nat Genet 49:119–124
Tezuka A, Yamamoto H, Yokoyama J, van Oosterhout C, Kawata M (2011) The MC1R gene in the guppy (Poecilia reticulata): genotypic and phenotypic polymorphisms. BMC Res Notes 4:31
Troemel ER, Chou JH, Dwyer ND, Colbert HA, Bargmann CI (1995) Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans. Cell 83:207–218
Villalta M, Estévez A, Bransden MP (2005) Arachidonic acid enriched live prey induces albinism in Senegalese sole (Solea senegalensis) larvae. Aquaculture 245:193–209
Villalta M, Estévez A, Bransden MP, Bell JG (2007) Arachidonic acid, arachidonic/eicosapentaenoic acid ratio, stearidonic acid and eicosanoids are involved in dietary-induced albinism in Senegal sole (Solea senegalensis). Aquac Nutr 13:1–9
Wei M, Xu WT, Li KM, Chen YD, Wang L, Meng L, Zhao FZ, Chen SL (2018) Cloning, characterization and functional analysis of dctn5 in immune response of Chinese tongue sole (Cynoglossus semilaevis). Fish Shellfish Immunol 77:392–401
Wolf Horrell EM, Boulanger MC, D'Orazio JA (2016) Melanocortin 1 receptor: structure, function, and regulation. Front Genet 7:95
Xu Y, Zhang XH, Pang YZ (2013) Association of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1) with melanic plumage color in Korean quails (Coturnix coturnix). Asian-Australas J Anim Sci 26:1518–1522
Yokoyama T, Silversides DW, Waymire KG, Kwon BS, Takeuchi T, Overbeek PA (1990) Conserved cysteine to serine mutation in tyrosinase is responsible for the classical albino mutation in laboratory mice. Nucleic Acids Res 18:7293–7298
You P, Hu H, Chen Y, Zhao Y, Yang Y, Wang T, Xing R, Shao Y, Zhang W, Li D, Chen H, Liu M (2016) Effects of melanocortin 3 and 4 receptor deficiency on energy homeostasis in rats. Sci Rep 6:34938
Zhang B, Zhao N, Jia L, Peng K, Che J, Li K, He X, Sun J, Bao B (2019) Seminal plasma exosomes: promising biomarkers for identification of male and pseudo-males in Cynoglossus semilaevis. Mar Biotechnol (NY)
Funding
This work was supported by grants from the Tianjin Natural Science Foundation (17JCQNJC15000), transformation project of Tianjin Agricultural Achievements (201604090), special funding for Modern Agricultural Industrial Technology System (CARS-47-Z01), Modern Industrial Technology System in Tianjin (ITTFRS2017011), and National Natural Science Foundation of China (31872546, 31472262), the China-ASEAN Maritime Cooperation Fund through the project “China-ASEAN Center for Joint Research and Promotion of Marine Aquaculture Technology”.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
All experiments were approved by the Animal Care Committee of Shanghai Ocean University and Tianjin Bohai Sea Fisheries Research Institute.
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Highlights
•Mc1r was characterized from the Cynoglossus semilaevis
•The expression of Mc1r in normal and melanistic C.semilaevis tissues is evaluated
•MC1R is crucial forTyrp1- and Mitf-mediated pigment synthesis in C.semilaevis, knocking down of Mc1r increases expression of the downstream genes Mitf and Tyrp1
Rights and permissions
About this article
Cite this article
Li, K., Zhao, N., Zhang, B. et al. Identification and characterization of the melanocortin 1 receptor gene (MC1R) in hypermelanistic Chinese tongue sole (Cynoglossus semilaevis). Fish Physiol Biochem 46, 881–890 (2020). https://doi.org/10.1007/s10695-019-00758-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10695-019-00758-8