McLennan R, Krull C E
Biological Sciences, University of Missouri-Columbia, 65211, USA.
Gene Expr. 2002;10(5-6):295-305. doi: 10.3727/000000002783992389.
Trunk neural crest cells delaminate from the dorsal neural tube and migrate on two distinct pathways: a dorsolateral route, between the ectoderm and somites,and a ventromedial route, through the somitic mesoderm. Neural crest cells that migrate ventromedially travel in a segmental manner through rostral half-somites, avoiding caudal halves. Recent studies demonstrate that various molecular cues guide the migration of neural crest cells, primarily by serving as inhibitors to premature pathway entry orby preventing neural crest from entering inappropriate territories. Trajectories of migrating trunk neural crest are well organized and generally linear in nature, suggesting that positive, migration-promoting factors may be responsible for this organized cell behavior. However, the identity of these factors and their function are not well understood. Here we examine the expression of members of the EphA subclass of receptor tyrosine kinases and ephrins using RT-PCR and immunocytochemistry. Neural crest cells express ephrins and EphA4 at distinct stages during their migration. In functional analyses, addition of ephrin-A2-, ephrin-A5-, and EphA4-Fc disrupted the segmental organization of trunk neural crest migration in explants: neural crest cells entered rostral and caudal halves of somites. Finally, to test the specific effects of these factors on cell behavior, neural crest cells were exposed in vitro to substrate-bound EphA and ephrin-As. Surprisingly, neural crest cells avoided ephrin-A2 or ephrin-A5 substrates; this avoidance was abolished by the addition of EphA4. Together, these data suggest that ephrin-As and EphA4 cooperate to positively promote the migration of neural crest cells through rostral half somites in vivo.
躯干神经嵴细胞从背侧神经管脱离，并沿两条不同的路径迁移：一条是背外侧路径，位于外胚层和体节之间；另一条是腹内侧路径，穿过体节中胚层。沿腹内侧迁移的神经嵴细胞以节段性方式穿过头侧半体节，避开尾侧半体节。最近的研究表明，各种分子信号主要通过作为过早进入路径的抑制剂或防止神经嵴进入不适当区域来引导神经嵴细胞的迁移。迁移的躯干神经嵴的轨迹组织良好，本质上通常是线性的，这表明正向的、促进迁移的因子可能负责这种有组织的细胞行为。然而，这些因子的身份及其功能尚不清楚。在这里，我们使用逆转录聚合酶链反应（RT-PCR）和免疫细胞化学方法检测受体酪氨酸激酶EphA亚类成员和ephrin的表达。神经嵴细胞在迁移的不同阶段表达ephrin和EphA4。在功能分析中，添加ephrin-A2、ephrin-A5和EphA4-Fc会破坏外植体中躯干神经嵴迁移的节段性组织：神经嵴细胞进入体节的头侧和尾侧半体节。最后，为了测试这些因子对细胞行为的具体影响，将神经嵴细胞在体外暴露于底物结合的EphA和ephrin-A。令人惊讶的是，神经嵴细胞避开ephrin-A2或ephrin-A5底物；添加EphA4可消除这种回避现象。这些数据共同表明，ephrin-A和EphA4协同作用，在体内正向促进神经嵴细胞通过头侧半体节迁移。
