Matsui Y, Zsebo K M, Hogan B L
Department of Cell Biology, Vanderbilt University Medical School, Nashville, Tennessee 37232-2172.
Nature. 1990 Oct 18;347(6294):667-9. doi: 10.1038/347667a0.
Mice carrying mutations at the W (Dominant white spotting) and Sl (Steel) loci develop abnormalities in three independent systems: neural crest-derived melanocytes, primordial germ cells and haematopoietic stem cells. Consequently, homozygotes of viable mutant alleles have white coats and are sterile and severely anaemic. Tissue recombination studies predict that the W gene is expressed cell autonomously, whereas the product of the Sl locus affects the microenvironment in which the stem cells migrate, proliferate and differentiate. The W locus encodes the protoncogene c-kit, a member of the tyrosine kinase receptor family. The haematopoietic growth factor SCF (stem cell factor) has been identified as the product of the Sl locus and a ligand for c-kit. Here, we report that SCF is expressed during embryogenesis in cells associated with both the migratory pathways and homing sites of melanoblasts, germ cells and haematopoietic stem cells. Both SCF and c-kit are also expressed in a variety of other tissues, including the brain and spinal cord, suggesting that the receptor-ligand system has additional roles in embryogenesis.
携带W(显性白斑)和Sl(Steel)位点突变的小鼠在三个独立系统中出现异常:神经嵴衍生的黑素细胞、原始生殖细胞和造血干细胞。因此,存活突变等位基因的纯合子有白色被毛,不育且严重贫血。组织重组研究预测,W基因在细胞内自主表达,而Sl位点的产物影响干细胞迁移、增殖和分化的微环境。W位点编码原癌基因c-kit,它是酪氨酸激酶受体家族的成员。造血生长因子SCF(干细胞因子)已被确定为Sl位点的产物和c-kit的配体。在这里,我们报告SCF在胚胎发育过程中在与黑素母细胞、生殖细胞和造血干细胞的迁移途径及归巢位点相关的细胞中表达。SCF和c-kit也在包括脑和脊髓在内的多种其他组织中表达,这表明受体-配体系统在胚胎发育中还有其他作用。