Activation of the receptor tyrosine kinase kit is required for the proliferation of melanoblasts in the mouse embryo
Activation of the receptor tyrosine kinase kit is required for the proliferation of melanoblasts in the mouse embryo
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DOI：
10.1006/dbio.1997.8738
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发表时间：
1997-12-01
影响因子：
2.7
通讯作者：
Jackson, IJ
中科院分区：
文献类型：
--
作者：
MacKenzie, MAF;Jordan, SA;Jackson, IJ
神经嵴来源的黑素细胞以及造血细胞和生殖细胞的发育受到 Kit 和 Mgf 基因突变的影响，从而导致显性斑点 (W) 或钢 (S1) 表型。 Mgf 编码 Kit 基因座编码的受体酪氨酸激酶的配体。 Kit(W-v)是一种发挥显性负效应的点突变，导致Kit受体的酪氨酸激酶活性大幅降低，并导致杂合动物特征性色素沉着表型，即毛色淡化、腹侧和头部出现白色斑点，脚和尾部色素沉着减少，以及轻微贫血。纯合动物缺乏皮毛色素沉着，并且严重贫血和不育。 Dct 是黑素细胞谱系细胞的标记。为了详细研究这些细胞，我们生成了在 Dct 启动子控制下携带 lacZ 报告基因的转基因小鼠系，并利用报告基因的胚胎表达在早期黑素细胞开始产生色素之前识别它们。我们的转基因系简化了小鼠胚胎中黑色素细胞的研究，并且通过将我们的小鼠与 Kit(W-v) 突变体杂交，我们已经能够确定黑色素细胞严重依赖 Mgf/Kit 相互作用的妊娠中期阶段。我们得出的结论是，未成熟黑素细胞的存活在 E11 之前主要取决于 Kit 信号传导，而在发育后期，Kit 在黑素细胞增殖中发挥着至关重要的作用。我们的数据并未描述黑素细胞迁移或分化对 Kit 的依赖性。 (C) 1997 年学术出版社。
The development of neural crest-derived melanocytes, as well as haematopoietic and germ cells, is affected by mutations of the Kit and Mgf genes, which lead to dominant spotting (W) or steel (S1) phenotypes. Mgf codes for the ligand of the receptor tyrosine kinase encoded by the Kit locus. Kit(W-v), a point mutation exerting a dominant negative effect, causes a substantial reduction in tyrosine kinase activity of the Kit receptor and leads to a characteristic pigmentation phenotype, namely dilute coat colour and a white ventral and head spot with reduced pigmentation of the feet and tail in the heterozygous animal, as well as slight anaemia. Homozygous animals lack coat pigmentation and are severely anaemic and infertile. Dct is a marker for cells of the melanoblast lineage. In order to study these cells in detail we have generated transgenic mouse lines carrying the lacZ reporter under the control of the Dct promoter and have used the embryonic expression of the reporter to identify early melanoblasts before they begin to produce pigment. Our transgenic lines have simplified the study of melanoblasts in the mouse embryo, and by crossing our mice with Kit(W-v) mutants we have been able to identify the midgestation stages at which melanoblasts rely critically on Mgf/Kit interactions. We conclude that the survival of immature melanoblasts depends crucially upon Kit signalling up until E11, and later in development Kit plays a vital role in melanoblast proliferation. Our data do not describe a dependence upon Kit for melanoblast migration or differentiation. (C) 1997 Academic Press.