Abstract

The site of action of piebald, a major spotting gene in the mouse, was investigated according to a method by which embryonic neural tube and skin of various genotypes were grafted in combination to White Leghorn chick embryo hosts. Melanoblasts from the embryonic neural tube migrated into the adjacent developing skin, and the importance of these two components in pattern formation was thereby analyzed. Combination grafts of neural tube and skin from solC57BL 6J embryos produced extensive pigmentation in the hair and dermis of the grafted skin and in the tissues of the host embryo. Grafts of normal neural tube and piebald skin yielded identical results. Grafts of pieblad neural tube and normal skin produced pigmentation only in the hair follicles. The dermis of the grafted skin and the host tissues were devoid of pigment. Melanoblasts of the piebald genotype therefore differentiated only in the tissue environment of the hair follicle. A descriptive study of the pigment content of the Harderian gland, ankle skin, leg musculature, membranous labyrinth of the ear, and the choroid layer of the eye was made of normal, s s , and heterozygous ( s + mice. Each of these tissues possessed melanocytes in large numbers in normal C57BL mice. A significant reduction of the pigment content of the Harderian gland, ankle skin, leg musculature, and choroid was found in s s mice. The melanocyte content of the membranous labyrinth was the same in both genotypes. Heterozygous mice were intermediate between these two groups in the pigment content of the leg musculature and the ankle skin. The results of this study place a determining role in the development of white spotting on the neural crest of piebald mice. A secondary but important factor is the tissue environment in which the melanoblast is developing. The following mechanism of action of the piebald gene is proposed. Piebald melanoblasts differ from the normal by being more sensitive to different levels of melanogenic stimuli in the various tissue environments of the mouse. Those tissues which have a low melanogenic activity therefore will lack melanocytes of the piebald genotype. Coat spotting may be due to the existence of similar regional differences in the skin to which piebald melanoblasts are more sensitive than normal.

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