Interaction and developmental activation of two neuroendocrine systems that regulate light‐mediated skin pigmentation

Abstract

Lower vertebrates use rapid light-regulated changes in skin colour for camouflage (background adaptation) or during circadian variation in irradiance levels. Two neuroendocrine systems, the eye/alpha-melanocyte-stimulating hormone (α-MSH) and the pineal complex/melatonin circuits, regulate the process through their respective dispersion and aggregation of pigment granules (melanosomes) in skin melanophores. During development, Xenopus laevis tadpoles raised on a black background or in the dark perceive less light sensed by the eye and darken in response to increased α-MSH secretion. As embryogenesis proceeds, the pineal complex/melatonin circuit becomes the dominant regulator in the dark and induces lightening of the skin of larvae. The eye/α-MSH circuit continues to mediate darkening of embryos on a black background, but we propose the circuit is shut down in complete darkness in part by melatonin acting on receptors expressed by pituitary cells to inhibit the expression of pomc, the precursor of α-MSH.

Seeing the light to change colour: An evolutionary perspective on the role of melanopsin in neuroendocrine circuits regulating light‐mediated skin pigmentation

“…Rising melatonin levels induce melanosome aggregation and skin whitening at night (dark), a response that is abolished in pinealectomized larvae (Figure b; Bagnara, , ). In X. laevis , the response occurs at developmental times in which melanopsin is already expressed in the eye and the pineal complex (Bertolesi et al., , ; Provencio et al., ; our own unpublished data). The circuits that control changes in skin colour appear segregated even early in development, in that background adaptation occurs independently of the pineal complex, whereas skin pigmentation responses to differences in illumination occur in the absence of the eye (Figure b).…”

“…In mammals, pupillary constriction (Chen et al, 2011;Gooley, Lu, Fischer, & Saper, 2003) and sleep induction Lupi et al, 2008) also depend on light activation of ipRGCs. It was only melanopsin expression by skin melanophores of LEI organisms that suggested a function in regulating pigmentation (Isoldi et al, 2005;Rollag et al, 2000), until we showed recently that retinal melanopsin in the eye indirectly regulates pigmentation through activation of a neuroendocrine circuit (Bertolesi, Hehr, & Mcfarlane, 2015;Bertolesi, Hehr, Munn, & McFarlane, 2016;Bertolesi, Song, Atkinson-Leadbeater, Yang, & McFarlane, 2017;Bertolesi, Vazhappilly, Hehr, & Mcfarlane, 2016). Indeed, ipRGCs regulate the secretion of melatonin (Lucas, Freedman, Muñoz, Garcia-Fernández, & Foster, 1999;Lupi et al, 2008;Sekaran et al, 2005) and α-MSH (Bertolesi et al, 2015), which modulate skin pigmentation of LEI and LPI organisms (Jenks, van Overbeeke, & McStay, 1977;Slominski, Tobin, Zmijewski, Wortsman, & Paus, 2008).…”

“…This is because during background adaptation, light acts directly at the level of the pineal gland to block melatonin synthesis (see Section 5; Kalsbeek et al, 2000;Klein, 2006;Perreau-Lenz, Kalsbeek, Van Der Vliet, Pevet, & Buijs, 2005). Indeed, in amphibians, background adaptation occurs in pinealectomized animals (Figure 3b; Bertolesi et al, 2017).…”

“…Certainly, levels of the two molecules are inversely correlated, with melatonin levels high and α-MSH levels low in winter when the nights are long, and increased α-MSH in the spring when the melatonin signal decreases ( Figure 4a). Further, the melatonin receptor Mel1a (MT1 in mammals) is expressed by α-MSH-synthesizing pituitary cells in adult (Wiechmann, Vrieze, & Wirsig-Wiechmann, 2003) and larval (Bertolesi et al, 2017) X. laevis, and the size of the pars intermedia pituitary, which increases in black background-adapted Xenopus (Corstens, Roubos, Jenks, & Van Erp, 2005;de Rijk et al, 1990), is reduced by melatonin treatment concomitant with skin lightening (Bertolesi et al, 2017). This ability of melatonin to reduce α-MSH secretion appears to be conserved in mammals.…”

Transcriptomics reveals the molecular processes of light-induced rapid darkening of the non-obligate cave dweller Oreolalax rhodostigmatus (Megophryidae, Anura) and their genetic basis of pigmentation strategy

“…It is commonly observed in the color change of fish, amphibians and reptiles. PCC is mainly regulated by hormones, whose release is responsive to light [ 20 ]. Hormones inducing pigment dispersion in frogs includes alpha-melanocyte-stimulating hormone (α-MSH), adrenocorticotropic hormone (ACTH) and melanin-concentrating hormone (MCH), while those induce pigment aggregation include melatonin and adrenaline [ 1 ].…”