Analysis of melanocyte precursors in Nf1 mutants reveals that MGF/KIT signaling promotes directed cell migration independent of its function in cell survival.
Analysis of melanocyte precursors in Nf1 mutants reveals that MGF/KIT signaling promotes directed cell migration independent of its function in cell survival.
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对 Nf1 突变体中黑素细胞前体的分析表明，MGF/KIT 信号传导促进定向细胞迁移，与其在细胞存活中的功能无关。
DOI：
10.1006/dbio.2001.0167
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Weston,JA
中科院分区：
文献类型：
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作者：
Wehrle-Haller,B;Meller,M;Weston,JA
在鸟类和小鼠胚胎中，神经嵴来源的黑素细胞前体（MP）从背侧神经管进入迁移分期区（MSA）。MP随后从MSA迁移到真皮肌节和上覆上皮之间的背外侧通路上。在小鼠胚胎中，MP表达受体酪氨酸激酶KIT，并需要其同源配体肥大细胞生长因子（MGF）才能生存和分化。在MP迁移开始之前，MGF在MSA中距离细胞一定距离的背外侧通路上表达，并且似乎是正常MP发育所需的。为了了解MGF是否仅为MP在该途径上的存活所需，或者它是否也为迁移提供方向性线索，我们使用在神经纤维蛋白（Nf 1）基因座携带靶向突变并因此缺乏RAS-GAP功能的小鼠，将该配体的化学吸引或运动原功能与存活分离。我们发现，NF 1突变的MP生存在体外和体内的MGF的情况下，NF 1突变的MP分散在MGF的存在下的横向迁移途径正常。相比之下，Nf 1突变的MP坚持在MSA的位置，但没有观察到的横向迁移途径在双突变小鼠，也缺乏MGF。我们的结论是MGF/KIT功能提供了一个信号，所需的定向迁移的MP在体内的侧通路，独立于其功能的生存。我们进一步建议MGF通过不涉及RAS的信号通路介导MP迁移。
Neural crest-derived melanocyte precursors (MPs) in avian and murine embryos emerge from the dorsal neural tube into a migration staging area (MSA). MPs subsequently migrate from the MSA on a dorsolateral pathway between the dermamyotome and the overlying epithelium. In mouse embryos, MPs express the receptor tyrosine kinase, KIT, and require its cognate ligand, Mast cell growth factor (MGF), for survival and differentiation. Prior to the onset of MP migration, MGF is expressed on the dorsolateral pathway at some distance from cells in the MSA and appears to be required for normal MP development. To learn if MGF is required solely for MP survival on this pathway, or if it also provides directional cues for migration, we uncoupled survival from chemoattractive or motogenic functions of this ligand using mice that carry a targeted mutation at the Neurofibromin (Nf1) locus and consequently lack RAS-GAP function. We show that Nf1-mutant MPs survive in the absence of MGF in vitro and in vivo and that Nf1-mutant MPs disperse normally on the lateral migration pathway in the presence of MGF. In contrast, Nf1-mutant MPs persist in the location of the MSA but are not observed on the lateral migration pathway in double-mutant mice that also lack MGF. We conclude that MGF/KIT function provides a signal required for directed migration of the MPs on the lateral pathway in vivo, independent of its function in survival. We further suggest that the MGF mediates MP migration through a signaling pathway that does not involve RAS.