Skin and Its Derivatives 



503 



'43; Rawles, '48; Horstadius, '50) is based 

 principally upon the following evidence: 

 (1) extirpation of the neural folds (includ- 

 ing the primordia of the crest) of neurulae 

 results in a total absence of pigment cells 

 from the operated trunk region; (2) isolated 

 neural folds produce numerous pigment cells 

 when cultured in vitro or (3) when trans- 

 planted to the flank of another embryo of the 

 same or of a different species. In the latter 

 case, the pigment cells which develop in 

 the foreign host are always of the donor 

 type. While the entire neural crest is po- 

 tentially capable of producing all of the 

 various types of pigment cells — melano- 

 phores, xanthophores, guanophores — found 

 in the body of an amphibian, it nevertheless 

 does exhibit regional differences as regards 

 the nvimber of these cells produced. The 

 great majority appear to come from the crest 

 of the trunk region (Niu, '47; Twitty, '49). 



In birds, as in amphibians, the neural 

 crest origin of the pigment cells (melano- 

 phores) has been unequivocally established 

 by a variety of experimental results. The 

 evidence briefly summarized is as follows: 

 (1) explants including the neural crest pro- 

 duce typical melanophores when cultured 

 in vitro (Dorris, '38); (2) melanophores dif- 

 ferentiate from isolates containing the crest, 

 or any of its migratory cells, when grafted 

 to the embryonic coelom (Eastlick, '39; Ris, 

 '41) or to the early limb bud (Dorris, '39; 

 Willier and Rawles, '40). Similar isolates 

 without the crest never prodvice pigment; 

 (3) neural crest cells grafted between em- 

 bryos of different species of fowl, or even 

 between wild birds and fowl, invariably pro- 

 duce melanophores of the donor type whose 

 activity in the feathers of the host is re- 

 corded in the form of a typical donor colora- 

 tion or pattern. 



Among mammals, the mouse embryo has 

 so far been the only representative in which 

 the origin of the pigment-forming cells has 

 been tested experimentally. The results are 

 clear cut, however, in showing that only 

 those tissues containing prospective neural 

 crest, histologically recognizable neural crest 

 or cells migrating from the neural crest, can 

 prodvice pigment in grafts (Rawles, '47). 



Thus the evidence has clearly established 

 the origin of pigment cells of amphibians, 

 birds, and mammals from the neural crest. 

 A similar origin is indicated also for the 

 lamprey (Newth, '51) and for the bony fishes 

 (Borcea, '09; Lopashov, '44; Orton, '53). It 

 is highly probable that the neural crest or 

 its equivalent, the dorsal neural border, is 



the source of pigment cells in all of the 

 vertebrates. Further proof would be welcome 

 for some of the lower forms. 



Migration of Pigment-forming Cells (Mel- 

 anoblasts) into the Skin. From their locus of 

 origin in the neural crest, prospective pig- 

 ment cells migrate gradually to all regions 

 of the body of the embryo. During this 

 period of dispersal they cannot be distin- 

 guished with certainty either morphologi- 

 cally or histologically from the other em- 

 bryonic cells with which they are associated. 

 Yet, by means of appropriate transplanta- 

 tion experiments, it has been demonstrated 

 clearly that they have reached all body re- 

 gions of a chick embryo by the fourth day 

 of incubation and all body regions of a mouse 

 embryo by the twelfth day of gestation — 

 long before there is any visible sign of pig- 

 mentation. As development proceeds and bio- 

 chemical conditions become sviitable for the 

 synthesis of melanin, these "colorless" cells 

 begin their characteristic differentiation and 

 henceforth are readily distinguishable from 

 surrounding cells. Observed differences in 

 the distribution patterns of these cells after 

 the differentiation of melanin pigment gran- 

 ules are not, however, necessarily a reflec- 

 tion of corresponding differences in their 

 original dispersal from the neural crest. 

 Recent evidence indicates that the character- 

 istic longitudinal stripes of certain larval 

 amphibians are formed by a secondary re- 

 arrangement of pigment cells originally 

 more widely scattered over the lateral sur- 

 faces of the somites (Rosin, '43; Twitty, '45). 

 Many prospective pigment cells remain un- 

 differentiated (colorless) for long periods — 

 until after metamorphosis in amphibians — 

 and some undoubtedly become located in 

 positions unfavorable for the synthesis of pig- 

 ment. Both the reactivity of the pigment 

 cells and the biochemical properties of the 

 skin vary not only with the species, but 

 even regionally within one individual. 



The mechanism by which precursor pig- 

 ment cells (melanoblasts) reach the skin 

 and other locations is by no means com- 

 pletely understood. While it is evident from 

 in vitro and other studies that these cells 

 are capable of independent movements, 

 much of their migratory activity is unques- 

 tionably dependent upon contact relationship 

 with certain other strains of cells and tissues. 

 The fact that pigment cells are found pri- 

 marily along surface membranes (basal 

 layer of the epidermis, parietal membranes, 

 etc.) is significant. The possibility also that 

 their final distribution may be affected some- 



