神经冠是伴随着脊椎动物起源而产生的新细胞类型。在原肠胚，神经板两侧与非神经外胚层交界处表达神经板边缘（NPB）特化模块。它们激活一套神经冠特化因子的表达，使NPB细胞分化为具有迁移能力和多潜能的神经冠细胞。最后，不同位置的神经冠细胞表达各种分化基因群，分化为多种细胞类型。“神经冠特化模块嵌入”假说认为，位于这个神经冠基因调控网络顶层的NPB特化模块可能在远古两侧对称动物中就已经存在。随着脊索动物的进化，神经冠特化因子变成被NPB特化模块调控，并且指派了分化基因群。但这一假说还缺乏证据。申请人的前期工作筛查了几乎所有保守的转录因子，发现线虫P和Q神经前体细胞不表达神经冠特化因子，但其细胞迁移和分化特异地受NPB特化模块调控。例如，NPB特化因子调控一个可能保守的分化基因群使Q细胞后代分化为机械感受神经元。以这些初步工作为基础，本课题将进一步验证“嵌入”假说并凝练为“嵌入原始二阶层”模型。

The origin of vertebrates was accompanied by the advent of a novel cell type: the neural crest. During gastrulation, the boundary between neural plate and non-neural ectoderm expresses Neural-Plate-Border(NPB) specification module. This in turn leads to specification of bona fide migratory and multi-potential neural crest cells via initiating the expression of Neural-Crest(NC) specification module. At last, neural crest cells in different locations expression various differentiation gene batteries and give rise to diverse cell types. It has been proposed that during early vertebrate evolution, the NC specification module might be interposed downstream of the NPB specification module and co-opt differentiation gene batteries pre-existing in various cell types. To test this ‘interposition’ hypothesis, we have examined nearly all conserved transcription factors in C. elegans. It was observed that P and Q neuroblasts do not express any examined NC specifier. However, their migration and differentiation are controlled by core NPB specifiers (Msx/vab-15, Pax3/7/pax-3 and Zic/ref-2). For example, Msx/vab-15 regulates the expression of a likely conserved differentiation gene battery (Brn3/unc-86, DRG11/alr-1, asic/mec-4 and vglut2/eat-4) to control the differentiation of Q neuroblasts to mechanosensory neurons (AVM/PVM). In another word, C. elegans may have two-layer hierarchy of rudimentary NC Gene Regulatory Network. Based on these preliminary data, we will confirm and improve the “NC specification module interposition” hypothesis.