EXPRESSION AND TRANSGENIC STUDIES OF THE MOUSE AGOUTI GENE PROVIDE INSIGHT INTO THE MECHANISMS BY WHICH MAMMALIAN COAT COLOR PATTERNS ARE GENERATED

Expression of the agouti gene from two different promoters, one active at the midpoint of the hair cycle and the other specific for the vent rum, is responsible for generating a range of mammalian pigmentation p atterns, We demonstrate that in postnatal mice transcripts from both p romoters are confined to the dermal papilla of hair follicles, as pred icted by classical transplantation experiments, Transcripts from the h air cycle promoter are detected in the embryonic whisker plate but not in other regions of the body before birth, whereas ventral-specific t ranscripts are detected in the ventral trunk of the embryo as well as ventral whisker plate, To investigate further the embryonic origins of adult pigmentation patterns, we carried out a detailed analysis of ag outi expression in the embryo, The ventral-specific agouti isoform is first expressed at E10,5 in neural crest-derived ventral cells of the second branchial arch, in anterior regions of the forelimb buds and in a narrow stripe of ventral mesenchyme, By E14,5 a continuous layer of expression is observed in the upper cells of the dermis, including ce lls of the developing dermal papillae, and covering the entire ventral surface of the head and trunk and dorsal surfaces of the distal forel imb and hindlimb, This expression pattern reflects the domain of yello w coloration evident in adult animals and suggests that the agouti gen e is regulated in part by factors responsible for establishing differe nces between the dorsal and ventral surfaces of the body during embryo genesis, To test the hypothesis that agouti is a paracrine signaling m olecule that can influence pigment production by hair follicle melanoc ytes when expressed by either dermis or epidermis, as suggested by rec ombination and transplantation experiments, we created transgenic anim als in which agouti is expressed in basal cells of the epidermis, Thes e animals display stripes of yellow hairs corresponding to regions of epidermal agouti expression, confirming that agouti signals melanocyte s to synthesize yellow pigment and providing direct evidence that it f unctions in a paracrine manner with a restricted radius of action.