Transcriptional regulation of NC precursor formation

描述（由申请人提供）：神经嵴细胞是一种多能性、迁移性、组织侵袭性的细胞，起源于脊椎动物胚胎的外胚层，在脊椎动物身体计划的发展中起着核心作用。许多毁灭性的癌症，包括黑色素瘤和神经母细胞瘤，都是神经嵴的癌症。此外，神经嵴细胞与转移性肿瘤细胞具有许多共同特征，这两种细胞类型具有共同的关键分子介质，包括蜗牛家族抑制因子和c-myc。

DESCRIPTION (provided by applicant): Neural crest cells are multi-potent, migratory, tissue-invasive cells that originate in the ectoderm of vertebrate embryos and play a central role in the development of the vertebrate body plan. A number of devastating cancers, including melanoma and neuroblastoma, are cancers of the neural crest. Moreover, neural crest cells share a number of general characteristics with metastatic tumor cells, and these two cell types have key molecular mediators in common, including Snail-family repressors and c-myc. This proposal seeks to exploit the considerable advantages of the Xenopus system in order to better understand the roles played by Snail-related factors and c-myc during normal neural crest development and in tumorigenesis, including the acquisition of invasiveness. The aims of the grant include: 1) determining the molecular mechanisms that underlie the distinct activities of Snail-family proteins during neural crest precursor formation, neural crest emigration, and during epithelial-to-mesenchymal transitions (EMTs) in tumor cells; 2) determining if c-myc regulates the expression of neural crest target genes by recruiting HAT activity to target promoters, and determining if Id3 functions as a Myc-effector during neural crest formation; 3) using cDNA macroarray-based gene discovery methods to identify the key transcriptional targets of c-myc and Snail-family repressors during neural crest precursor cell formation, and during the onset of neural crest migration and 4) testing the hypothesis that such targets will also play roles in tumor progression by examining the expression of these factors, and the effects of over-expressing these factors, in a panel of epithelial tumor cell lines