Table_3_Molecular Events Controlling Cessation of Trunk Neural Crest Migration and Onset of Differentiation.docx

Neural crest cells (NCC) migrate extensively in vertebrate embryos to populate diverse derivatives including ganglia of the peripheral nervous system. Little is known about the molecular mechanisms that lead migrating trunk NCC to settle at selected sites in the embryo, ceasing their migration and initiating differentiation programs. To identify candidate genes involved in these processes, we profiled genes up-regulated in purified post-migratory compared with migratory NCC using a staged, macroarrayed cDNA library. A secondary screen of in situ hybridization revealed that many genes are specifically enhanced in neural crest-derived ganglia, including macrophage migration inhibitory factor (MIF), a ligand for CXCR4 receptor. Through in vivo and in vitro assays, we found that MIF functions as a potent chemoattractant for NCC. These results provide a molecular profile of genes expressed concomitant with gangliogenesis, thus, offering new markers and potential regulatory candidates involved in cessation of migration and onset of differentiation.

神经嵴细胞（NCC）在脊椎动物胚胎中广泛迁移，以充填包括外周神经系统神经节在内的多种衍生物。关于迁移性主干NCC在胚胎中选择性位点定居、终止迁移并启动分化程序的分子机制知之甚少。为识别参与这些过程的候选基因，我们采用分阶段、宏阵列化的cDNA库，对与纯化后的迁移性NCC相比上调的基因进行了分析。通过原位杂交的二次筛选，发现许多基因在神经嵴衍生的神经节中特异性增强，包括巨噬细胞迁移抑制因子（MIF），CXCR4受体的配体。通过体内和体外实验，我们发现MIF作为一种高效的趋化因子，对NCC具有作用。这些结果提供了与神经节发生同时表达的基因分子图谱，从而为迁移终止和分化启动过程中的新标记和潜在调节候选者提供了新的见解。