TACTICS IN PIGMENT-CELL RESEARCH 331 



Whereas in all species so far investigated (for example, mouse, rat, guinea pig, and 

 rabbit) the hair bulbs of white spots are characterized by matrices consisting of regularly 

 arranged cells of equal size, albino hair follicles contain, in addition, many large clear 

 cells in their upper bulb region. Histologic observations suggested that these hyaline 

 cells are amelanotic melanocytes, that is, melanocytes which are in every respect 

 normal except for their inability to synthesize melanin, since lightly pigmented geno- 

 types exhibit the same type of cell, except that there are pigment granules present in 

 the cytoplasm. Furthermore, Quevedo 1033 found that the melanocytes of intensely 

 pigmented mice, artificially depigmented by biotin deficiency, are similar in morpho- 

 logy to the follicular clear cells of the albino. To establish, beyond doubt, the identity 

 of these cells a determination of their embryologic origin was required. 



In the mouse, melanoblasts originate from the neural crest and migrate to their 

 definitive positions in the skin during the eighth to twelfth day of embryonic develop- 

 ment. This was established by Rawles 1040 ' 1041 who transplanted various portions of 

 potentially pigmented embryos to the celomic cavity of embryonic chicks and observed 

 the development of melanocytes from them. By this procedure she demonstrated that 

 there was an anterior to posterior mediolateral spread of neural-crest cells. For 

 example, melanocyte differentiation from 8.5- to 9-day-old embryonic transplants to 

 the chick celom depended on the presence of the neural tube, whereas with 10.5-day-old 

 embryos, skin ectoderm and adhering mesoderm from any level of the trunk, but not 

 from the limb bud, gave rise to pigmented hairs. The limb buds receive their neural 

 crest component during the eleventh day of development. 



Using an essentially similar procedure with the exception that the spleen of the 

 adult mouse instead of the chick embryo celom was used as the site for explants, it was 

 possible to prove conclusively that clear cells, like melanocytes, arise from the neural 

 crest. The absence of neural crest cells in the transplanted embryonic tissue was 

 associated with the failure of clear cells to appear in the hair bulbs of the developing 

 grafts. In the design of these experiments care was taken to utilize histocompatible 

 donor-host combinations which were readily available. 1206 



Whereas albinism appears to stem from an inherited metabolic defect — almost 

 certainly a failure of tyrosinase synthesis — in melanocytes which are otherwise present 

 in normal numbers and distribution, the basis of white spotting is still unknown. It is 

 obvious that white spotting could not have the same etiology as albinism, since in white- 

 spotted animals the ability to synthesize tyrosinase is present in some of the cells of the 

 body. This becomes even more apparent from the fact that hair bulbs of white- 

 spotted areas appear to lack clear cells and are indistinguishable from those which 

 develop in skin experimentally deprived of neural-crest cells. Consequently, it can be 

 assumed that a white spot results either from the absence of melanoblasts or from their 

 failure to differentiate in a particular area. If white spotting does result from a 

 localized environmental effect which inhibits the differentiation of melanoblasts 

 present in the spotted area, one would expect to obtain functional melanocytes from 

 these arrested cells if they are artificially introduced into an environment known to be 



