Two distinct types of mouse melanocyte: differential signaling requirement for the maintenance of non-cutaneous and dermal versus epidermal melanocytes

Abstract

Unlike the thoroughly investigated melanocyte population in the hair follicle of the epidermis, the growth and differentiation requirements of the melanocytes in the eye, harderian gland and inner ear -the so-called non-cutaneous melanocytes -remain unclear. In this study, we investigated the in vitro and in vivo effects of the factors that regulate melanocyte development on the stem cells or the precursors of these non-cutaneous melanocytes. In general, a reduction in KIT receptor tyrosine kinase signaling leads to disordered melanocyte development. However, melanocytes in the eye, ear and harderian gland were revealed to be less sensitive to KIT signaling than cutaneous melanocytes. Instead, melanocytes in the eye and harderian gland were stimulated more effectively by endothelin 3 (ET3) or hepatocyte growth factor (HGF) signals than by KIT signaling, and the precursors of these melanocytes expressed the lowest amount of KIT. The growth and differentiation of these non-cutaneous melanocytes were specifically inhibited by antagonists for ET3 and HGF. In transgenic mice induced to express ET3 or HGF in their skin and epithelial tissues from human cytokeratin 14 promoters, the survival and differentiation of non-cutaneous and dermal melanocytes, but not epidermal melanocytes, were enhanced, apparently irrespective of KIT signaling. These results provide a molecular basis for the clear discrimination between non-cutaneous or dermal melanocytes and epidermal melanocytes, a difference that might be important in the pathogenesis of melanocyte-related diseases and melanomas.

Biological and mathematical modeling of melanocyte development

“…We conclude that both surrounding environment and genetic context influence the proliferation rate of melanoblasts during development. Those findings are consistent with those of Kunisada, suggesting that specific factors influence melanocyte survival/growth/differentiation as a function of their location in the skin (Aoki et al, 2009). This model provided no evidence, either mathematical or experimental, for a second major wave of melanoblast production, at the body location and stages of development analyzed (Adameyko et al, 2009;Jordan and Jackson, 2000).…”

Gene Duplication of endothelin 3 Is Closely Correlated with the Hyperpigmentation of the Internal Organs (Fibromelanosis) in Silky Chickens

“…In the case of Aves, EDNRB2 is thought to be important for melanoblast migration toward the usual "dorsolateral" pathway (Pla et al 2005;Harris et al 2008). On the other hand, Aoki et al (2009) demonstrated that noncutaneous and dermal melanocytes are more sensitive to EDN3 for growth and differentiation compared with epidermal melanocytes. In Silky fowl, excess EDN3 may affect only the proliferation of the dermal melanocyte cell lineage during the early differentiating stage.…”

Induced haploinsufficiency of Kit receptor tyrosine kinase impairs brain development

“…With minor modifications, the method for the induction of neural lineage was the same as previously described (41,42). For differentiation, 1,000 trypsinized ES cells were inoculated on a monolayer of PA6 cells previously seeded on 6-well plates (BD Falcon).…”

“…The cultures were also exposed to 20 pM cholera toxin (Wako) from days 0 to 3, and the medium was changed every 3 days. In some experiments, 100 ng/ml recombinant Kitl (BioLegend) and 10 μg/ml rat monoclonal antibody ACK2, which can block Kit function (42,43), were added into the culture on the indicated days. In the indicated experiment, Rosa26::rtTA; Col1a1::tetO-Cre; Kit 2lox/+ ES cells were treated with 2 μg/ml doxycycline.…”