Stripes and belly-spots—A review of pigment cell morphogenesis in vertebrates

Abstract

Pigment patterns in the integument have long-attracted attention from both scientists and nonscientists alike since their natural attractiveness combines with their excellence as models for the general problem of pattern formation. Pigment cells are formed from the neural crest and must migrate to reach their final locations. In this review, we focus on our current understanding of mechanisms underlying the control of pigment cell migration and patterning in diverse vertebrates. The model systems discussed here -chick, mouse, and zebrafish -each provide unique insights into the major morphogenetic events driving pigment pattern formation. In birds and mammals, melanoblasts must be specified before they can migrate on the dorsolateral pathway. Transmembrane receptors involved in guiding them onto this route include EphB2 and Ednrb2 in chick, and Kit in mouse. Terminal migration depends, in part, upon extracellular matrix reorganization by ADAMTS20. Invasion of the ectoderm, especially into the feather germ and hair follicles, requires specific signals that are beginning to be characterized. We summarize our current understanding of the mechanisms regulating melanoblast number and organization in the epidermis. We note the apparent differences in pigment pattern formation in poikilothermic vertebrates when compared with birds and mammals. With more pigment cell types, migration pathways are more complex and largely unexplored; nevertheless, a role for Kit signaling in melanophore migration is clear and indicates that at least some patterning mechanisms may be highly conserved. We summarize the multiple factors thought to contribute to zebrafish embryonic pigment pattern formation, highlighting a recent study identifying Sdf1a as one factor crucial for regulation of melanophore positioning. Finally, we discuss the mechanisms generating a second, metamorphic pigment pattern in adult fish, emphasizing recent studies strengthening the evidence that undifferentiated progenitor cells play a major role in generating adult pigment cells.

Differentiated melanocyte cell division occurs in vivo and is promoted by mutations in Mitf

“…Unlike in mammals, zebrafish maintain the potential for extensive regeneration in many tissues (O'Reilly-Pol and Johnson, 2009;Poss, 2007), and it is possible that differentiated melanocyte division is specific to zebrafish. Nonetheless, the molecular machinery that controls melanocyte development is highly conserved (Kelsh et al, 2009) and suggests that our observations in zebrafish may be relevant to stem cell and differentiation-based therapy in melanoma, and in melanocyte regeneration in vitiligo.…”

“…For melanocytes, differentiation involves cell shape changes, the expression of pigmentation enzymes and the generation of melanins to colour the skin, hair and eyes (Kelsh et al, 2009;Levy et al, 2006). In mouse development, unpigmented melanoblasts first undergo extensive proliferation in the dermis prior to migration into the epidemis, followed by rapid expansion in the epidermis before localizing to the hair follicle (Jordan and Jackson, 2000;Mackenzie et al, 1997;Nishikawa et al, 1991).…”

The neural crest

“…Further patterning of NC cells into distinct streams and their precise targeting to specific tissues are controlled by a plethora of negative and positive guidance cues (Alfandari et al, 2010;Kelsh et al, 2009;Kirby and Hutson, 2010;Kulesa et al, 2010;Kuo and Erickson, 2010;Kuriyama and Mayor, 2008;Sasselli et al, 2012;Theveneau and Mayor, 2012).…”

“…Trunk NC cell migration is divided into two alternative paths (Kelsh et al, 2009;Kuo and Erickson, 2010): a dorsolateral pathway that is mostly used by NC cells of the pigment cell lineage, and a ventromedial route used by NC cells forming the trunk PNS. Admittance into the dorsolateral route is mostly controlled by endothelin and Eph/ephrin signalling.…”

Migration des cellules du lignage mélanocytaire

“…Certains des gènes identifiés comme responsables de la migration chez la souris, tel le gène Kit, sont également impliqués dans ce phénomène chez le poisson-zèbre. Cependant, leur fonction diffère à cause de la complexité de la mélanogenèse chez les poissons ou les amphibiens qui repose sur l'existence d'au moins quatre types cellulaires (mélanoblastes, leucoblastes, xanthoblastes et iridoblastes) migrant selon des voies différentes et encore mal explorées [7]. Chez le poulet, le facteur de transcription FoxD3 régule la formation des mélanoblastes en réprimant la migration dorso-latérale des CCN.…”