Expression and transgenic studies of the mouse agouti gene provide insight into the mechanisms by which mammalian coat color patterns are generated.
Expression and transgenic studies of the mouse agouti gene provide insight into the mechanisms by which mammalian coat color patterns are generated.
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DOI：
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发表时间：
1995-10
期刊：
影响因子：
4.6
通讯作者：
S. Millar;M. Miller;M. Stevens;G. Barsh
中科院分区：
文献类型：
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作者：
S. Millar;M. Miller;M. Stevens;G. Barsh
刺豚鼠基因由两个不同的启动子表达，一个在毛发周期的中点活跃，另一个则针对腹腔，负责产生一系列哺乳动物色素沉着模式。我们证明，在出生后的小鼠中，来自两个启动子的转录物仅限于毛囊的真皮乳头，正如经典移植实验所预测的那样。来自毛发周期启动子的转录物在胚胎须板中检测到，但在出生前的身体其他区域中未检测到，而腹侧特异性转录物在胚胎的腹侧干和腹侧须板中检测到。为了进一步研究成人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。腹侧特异性刺豚鼠亚型首先在第二鳃弓神经嵴衍生的腹侧细胞、前肢芽的前部区域和腹侧间质的窄带中的 E10.5 处表达。到E14.5，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的细胞，并且覆盖头部和躯干的整个腹侧表面以及远端前肢和后肢的背侧表面。这种表达模式反映了成年动物中明显的黄色区域，并表明刺豚鼠基因部分受到胚胎发生过程中身体背侧和腹侧表面之间建立差异的因素的调节。为了验证刺豚鼠是一种旁分泌信号分子，当真皮或表皮表达时，可以影响毛囊黑素细胞色素产生的假设，正如重组和移植实验所表明的那样，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。这些动物表现出与表皮刺鼠表达区域相对应的黄色毛发条纹，证实刺鼠向黑素细胞发出合成黄色素的信号，并提供直接证据表明它以旁分泌方式发挥作用，作用半径有限。
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.