Mitochondria are More Numerous and Smaller in Pink-Eyed Dilution Melanoblasts and Melanocytes Than in Wild-Type Melanocytes in the Neonatal Mouse Epidermis

Abstract

The mouse pink-eyed dilution (p) locus is known to control the melanin content in melanocytes. However, it was not known whether the p gene is involved in regulating the proliferation and differentation of melanocytes during development, especially the biogenesis of melanosomes and other organelles. Epidermal cell suspensions of neonatal dorsal skin derived from mice wild type for the p locus (black, C57BL/10JHir-P/P) and their congenic mutant phenotype (pink-eyed dilution, C57BL/10JHir-p/p) were cultured in serum-free melanocyte-proliferation medium (MDMD). The supplement of additional L-tyrosine (Tyr) into the MDMD stimulated the differentiation of p/p melanoblasts into melanocytes. Electron microscopy revealed that in p/p melanoblasts and melanocytes treated with L-Tyr, the number of stage II and III melanosomes dramatically increased. Moreover, p/p melanoblasts possessed smaller but more numerous mitochondria than P/P melanocytes. The treatment of p/p melanoblasts and melanocytes with L-Tyr decreased the number of mitochondria. The supplement of 2, 4-dinitrophenol (DNP), an inhibitor of mitochondrial function, into the MDMD stimulated both the proliferation and differentiation of p/p melanoblasts. Simultaneous treatment of DNP and L-Tyr dramatically stimulated the differetiation of p/p melanocytes. These results suggest that L-Tyr and some unknown factors related to mitochondrial function may influence the differentiation of melanoblasts in the epidermis of p/p mice.

How are proliferation and differentiation of melanocytes regulated?

“…Pink‐eyed dilution melanoblasts possess smaller but more numerous mitochondria than black melanocytes (Hirobe et al., 2002). Treatment of p/p melanoblasts with l‐ Tyr decreased the number of mitochondria (Hirobe et al., 2008). Media supplemented with 2,4‐dinitrophenol (DNP), an inhibitor of mitochondrial function, stimulated both proliferation and differentiation of p/p melanoblasts, and simultaneous DNP and l‐ Tyr treatment dramatically induced differentiation of p/p melanocytes (Hirobe et al., 2008).…”

“…Treatment of p/p melanoblasts with l‐ Tyr decreased the number of mitochondria (Hirobe et al., 2008). Media supplemented with 2,4‐dinitrophenol (DNP), an inhibitor of mitochondrial function, stimulated both proliferation and differentiation of p/p melanoblasts, and simultaneous DNP and l‐ Tyr treatment dramatically induced differentiation of p/p melanocytes (Hirobe et al., 2008). These results suggest that the p allele is involved in regulating the function of mitochondria.…”

The mouse pink‐eyed dilution allele of the P‐gene greatly inhibits eumelanin but not pheomelanin synthesis

“…Moreover, in p ⁄ p melanoblasts, only a few stage I and II melanosomes were observed, whereas in p ⁄ p melanocytes treated with L-Tyr, the number of stage II and III melanosomes increased dramatically (Hirobe et al, 2002b). It was also reported that p ⁄ p melanoblasts possessed smaller but more numerous mitochondria than P ⁄ P melanocytes (Hirobe et al, 2008). Treatment of p ⁄ p melanoblasts with L-Tyr decreased the number of mitochondria (Hirobe et al, 2008).…”

“…It was also reported that p ⁄ p melanoblasts possessed smaller but more numerous mitochondria than P ⁄ P melanocytes (Hirobe et al, 2008). Treatment of p ⁄ p melanoblasts with L-Tyr decreased the number of mitochondria (Hirobe et al, 2008). A 'melanoblast' is defined here as an unpigmented cell that possesses no tyrosinase activity.…”

“…The addition of 2,4-dinitrophenol (DNP), an inhibitor of mitochondrial function, into culture medium stimulated both proliferation and differentiation of p ⁄ p melanoblasts (Hirobe et al, 2008). Simultaneous treatment of DNP and L-Tyr dramatically induced the differentiation of p ⁄ p melanocytes (Hirobe et al, 2008). These results suggest that the p allele is involved in regulating the function of mitochondria.…”