Neural crest-directed gene transfer demonstrates Wnt1 role in melanocyte expansion and differentiation during mouse development
Neural crest-directed gene transfer demonstrates Wnt1 role in melanocyte expansion and differentiation during mouse development
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DOI：
10.1073/pnas.97.18.10050
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发表时间：
2000-08-29
影响因子：
11.1
通讯作者：
Pavan, WJ
中科院分区：
文献类型：
--
作者：
Dunn, KJ;Williams, BO;Pavan, WJ
Wnt 1信号转导被认为是参与神经嵴源性黑素细胞（NC-M）发育的一个因素。Wnt 1和Wnt 3a缺陷的小鼠在包括NC-Ms的躯干神经嵴衍生物中具有显著缺陷。我们使用Wnt信号传导基因的细胞系定向基因靶向来检查Wnt信号传导在小鼠神经嵴发育中的作用。通过在表达逆转录病毒受体tv-a的转基因小鼠系中用亚群A禽白血病病毒载体感染，将基因表达导向细胞谱系。我们分析了在表达nestin的神经前体细胞（Ntva系）或表达多巴色素互变异构酶（DCT）的黑素母细胞（DCTtva系）中携带tva的转基因小鼠。我们通过两种方式过度刺激Wnt信号：将Wnt 1定向基因转移到Ntva（+）细胞和将β-连环蛋白转移到DCTtva（+）NC-M前体细胞。观察到NC-M [黑色素（+）和酪氨酸酶相关蛋白1（TYRP 1）（+）细胞]的数量、黑色素-TYRP 1（+）细胞向黑色素（+）TYRP 1（+）NC-M的分化以及每个NC-M的色素沉着强度显著增加。这些数据与Wnt 1信号传导参与发育中的小鼠胚胎中迁移NC-M的扩增和分化一致。使用谱系定向基因靶向将允许解剖参与NC发育的信号传导分子，并且适用于其他哺乳动物发育系统。
Wnt1 signaling has been implicated as one factor involved in neural crest-derived melanocyte (NC-M) development. Mice deficient for both Wnt1 and Wnt3a have a marked deficiency in trunk neural crest derivatives including NC-Ms, We have used cell lineage-directed gene targeting of Wnt signaling genes to examine the effects of Wnt signaling in mouse neural crest development. Gene expression was directed to cell lineages by infection with subgroup A avian leukosis virus vectors in lines of transgenic mice that express the retrovirus receptor tv-a. Transgenic mice with tva in either nestin-expressing neural precursor cells (line Ntva) or dopachrome tautomerase (DCT)-expressing melanoblasts (line DCTtva) were analyzed, We overstimulated Wnt signaling in two ways: directed gene transfer of Wnt1 to Ntva(+) cells and transfer of beta-catenin to DCTtva(+) NC-M precursor cells, In both methods, NC-M expansion and differentiation were effected. Significant increases were observed in the number of NC-Ms [melanin(+) and tyrosinase-related protein 1 (TYRP1)(+) cells], the differentiation of melanin-TYRP1(+) cells to melanin(+) TYRP1(+) NC-Ms, and the intensity of pigmentation per NC-M. These data are consistent with Wnt1 signaling being involved in both expansion and differentiation of migrating NC-Ms in the developing mouse embryo, The use of lineage-directed gene targeting will allow the dissection of signaling molecules involved in NC development and is adaptable to other mammalian developmental systems.