TACTICS IN PIGMENT-CELL RESEARCH 329 



dorsal and ventral sides of the animal, ventrality appearing to favor yellow pigment 

 formation. On the dorsum the order of dominance is A y > A w = A > a 1 = a > a e , 

 whereas on the ventrum A w and a 1 are dominant to A. Thus the phenotype in 

 Aa l animals is indistinguishable from that produced in the yellow-bellied agouti, 

 A w — 



There are two possible mechanisms by means of which the alleles at the agouti 

 locus produce their effect: (1) by acting autonomously within the hair-bulb melano- 

 blasts themselves, in which case each agouti-series genotype would differ from the others 

 at the level of its melanoblasts, or (2) by producing their effects by altering the follicular 

 environment in some manner which, in turn, affects the expression of what are essen- 

 tially equally susceptible and similar melanoblasts common to all genotypes. 



Availability of the appropriate isogenic color stocks and their F 1 hybrids has made 

 it possible to discriminate between these two alternative mechanisms. This was done 

 by transplanting histocompatible skin from near-term or newborn donors to neonatal 

 recipients which differed in respect to the nature (agouti-locus constitution) and 

 intensity (other loci) of their future pigmentation. Thus the analysis depended on the 

 mode of expression of potentially intensely pigmented melanoblasts of one agouti-locus 

 constitution when incorporated, following their migration, into the developing follicles 

 of a graft which was not only of a different agouti-locus genotype or of a different 

 tract origin (for example, ventral to dorsal), but with hairs (when pigmented by the 

 melanoblasts indigenous in the graft) either light in color or white. 



For example, an experiment was conducted with an inbred stock of yellow animals 

 consisting of two genotypes, A y ac e c e and aac e c e . Animals of the A y ac e c e genotype 

 appear as black-eyed whites, and aac e c e animals are light gray in color. Newborn 

 animals from this light-colored stock provided skin grafts, while the hosts for these 

 grafts were intensely pigmented, histocompatible yellow (A y aCc e ) and black (aaCc e ) 

 animals obtained by crossing A y ac e c e animals with those of the C57BL/6 (aaCC) inbred 

 strain. Under these conditions it was found that when genotypically black melano- 

 blasts, aaCc e , migrated into the genetically yellow but phenotypically non-pigmented 

 A y ac e c e hair bulbs of the grafted skin, intensely pigmented yellow hairs were produced. 

 Conversely, when yellow melanoblasts, A y aCc e , migrated into normally lightly pig- 

 mented aac e c e hair bulbs, black hairs resulted. 



Similar studies have been conducted with other host-donor combinations at the 

 agouti locus. 1202 - 1203 ' 1208 All the results are consistent with the hypothesis that the 

 agouti-locus genotype of the receiving hair follicle determines whether eumelanin or 

 phaeomelanin or both (the agouti pattern) will be produced by its melanocytes. 

 Furthermore, the results also indicate that this expression of genie activity is dependent 

 not only upon the genotype of the follicular environment but also upon the location of 

 this environment on the integument, for example, whether it is on the dorsum or 

 ventrum of the animal. These experiments, made possible only by the availability 

 of the proper isogenic strains, show that at least some of the genes affecting hair color 

 act indirectly upon the melanocytes via the milieu of the hair follicle. It is hoped that 



