The Origin of Specific Proteins 99 



— occur in mice and in other vertehrates as well. Both types must have 

 arisen from a common precursor cell at some early stage in embryonic 

 development. The progeny of this cell later separated into two groups, 

 each proceeding down its own distinct pathway of embryonic develop- 

 ment. One group gave rise to the outer wall of the optic cup, which 

 transforms into the pigmented retina. These are the epithelial melano- 

 cytes. The other group gave rise to the neural crest, from which 

 melanoblasts migrate to many different tissues, such as those of the 

 hair follicles. In these terminal tissue sites they receive differentiating 

 stimuli from the surrounding cells and are thus enabled to complete 

 their transformation into mature dendritic melanocytes. 



Gene-controlled metabolites from both the embryonic melanoblast 

 and from the cells of the tissue environment are jointly required to 

 bring a melanoblast to full maturity as a pigmented melanocyte. We 

 might reasonably expect, therefore, that some genes affecting melano- 

 cyte differentiation would operate primarily within the melanoblast 

 while others would be expressed in the cells of the tissue environment. 

 This expectation is realized. 



Since epithelial and dendritic melanocytes reside in quite different 

 tissue environments, they commonly respond differentially to those 

 mutant genes that operate through the tissue environment. For ex- 

 ample, in mice carrying the gene for yellow hair, the dendritic 

 melanocytes are induced to synthesize yellow pigment when in the 

 hair follicles, but the epithelial melanocytes of the eye continue to 

 make black pigment. The early steps in the differentiation of the two 

 types of melanocyte can also be controlled by different genes. 



Black-eyed white mice carry a gene that prevents the differentiation 

 of all dendritic melanocytes while permitting the differentiation of 

 the pigmented retina. Similarly the genes for eyelessness prevent the 

 appearance of epithelial melanocytes while leaving unaffected the 

 development of dendritic melanocytes. However, many genes affect 

 both types of melanocyte, particularly those genes which control the 

 terminal stages of pigment formation. The albino gene, for example, 

 suppresses melanin pigment formation in all melanocytes by prevent- 

 ing the synthesis of tyrosinase. Likewise the black or brown color of 

 pigmented animals is determined by the same gene equally in both 

 kinds of melanocytes. 



Melanin pigment is produced in a complex cell organelle called a 

 melanosome (Moyer, 1961). The development of melanosomes is an 

 indispensable condition for the normal synthesis of the specific pro- 

 tein, tyrosinase. Apparently the protein fibrils of the melanosome are 

 the exclusive sites of tyrosinase activity. Figure 1 shows a sequence 



