Millar S E, Miller M W, Stevens M E, Barsh G S
Department of Pediatrics, Stanford University School of Medicine, CA 94305-5428, USA.
Development. 1995 Oct;121(10):3223-32. doi: 10.1242/dev.121.10.3223.
Expression of the agouti gene from two different promoters, one active at the midpoint of the hair cycle and the other specific for the ventrum, is responsible for generating a range of mammalian pigmentation patterns. We demonstrate that in postnatal mice transcripts from both promoters are confined to the dermal papilla of hair follicles, as predicted by classical transplantation experiments. Transcripts from the hair cycle promoter are detected in the embryonic whisker plate but not in other regions of the body before birth, whereas ventral-specific transcripts 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 agouti 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 cells of the developing dermal papillae, and covering the entire ventral surface of the head and trunk and dorsal surfaces of the distal forelimb and hindlimb. This expression pattern reflects the domain of yellow coloration evident in adult animals and suggests that the agouti gene is regulated in part by factors responsible for establishing differences between the dorsal and ventral surfaces of the body during embryogenesis. To test the hypothesis that agouti is a paracrine signaling molecule that can influence pigment production by hair follicle melanocytes when expressed by either dermis or epidermis, as suggested by recombination and transplantation experiments, we created transgenic animals in which agouti is expressed in basal cells of the epidermis. These animals display stripes of yellow hairs corresponding to regions of epidermal agouti expression, confirming that agouti signals melanocytes to synthesize yellow pigment and providing direct evidence that it functions in a paracrine manner with a restricted radius of action.
刺豚鼠基因从两个不同的启动子表达，一个在毛发生长周期的中点活跃，另一个特定于腹部，这负责产生一系列哺乳动物的色素沉着模式。我们证明，正如经典移植实验所预测的那样，在出生后的小鼠中，来自两个启动子的转录本都局限于毛囊的真皮乳头。来自毛发生长周期启动子的转录本在胚胎触须板中被检测到，但在出生前身体的其他区域未被检测到，而腹部特异性转录本在胚胎的腹侧躯干以及腹侧触须板中被检测到。为了进一步研究成年色素沉着模式的胚胎起源，我们对胚胎中的刺豚鼠表达进行了详细分析。腹部特异性刺豚鼠异构体首先在胚胎第10.5天在第二鳃弓的神经嵴衍生的腹侧细胞、前肢芽的前部区域以及腹侧间充质的一条窄带中表达。到胚胎第14.5天，在真皮的上层细胞中观察到连续的表达层，包括发育中的真皮乳头细胞，并覆盖头部和躯干的整个腹侧表面以及前肢和后肢远端的背侧表面。这种表达模式反映了成年动物中明显的黄色着色区域，并表明刺豚鼠基因部分受负责在胚胎发育过程中建立身体背腹表面差异的因素调控。为了检验如下假设，即如重组和移植实验所表明的，刺豚鼠是一种旁分泌信号分子，当由真皮或表皮表达时可影响毛囊黑素细胞的色素产生，我们创建了转基因动物，其中刺豚鼠在表皮的基底细胞中表达。这些动物显示出与表皮刺豚鼠表达区域相对应的黄色毛发条纹，证实刺豚鼠向黑素细胞发出合成黄色色素的信号，并提供了直接证据表明它以旁分泌方式起作用，作用半径有限。
