Control of neural crest cell migration via signalling molecules (BMP-4, Noggin, eFGF, Wnts) in the Mexican axolotl (Ambystoma mexicanum)

通过信号分子（BMP-4、Noggin、eFGF、Wnts）控制墨西哥蝾螈（Ambystoma mexicanum）中的神经嵴细胞迁移

• 批准号: 5368351
• 负责人: Professor Dr. Hans-Henning Epperlein
• 金额: --
• 依托单位: Institut für Anatomie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5368351?language=en
• 关键词: Control; neural; crest; cell; migration

The migration of neural crest (NC) cells is a key event during vertebrate development. Wild-type (dark) and white mutant embryos of the Mexican axolotl (Ambystoma mexicanum) provide a unique experimental system for studying lateral NC cell migration. In dark embryos NC-derived pigment cells migrate laterally under the epidermis. This migration is inhibited in the white mutant. The molecular nature of this defect is not known. The aim of this proposal is to investigate whether the TGF-ß protein BMP-4, its antagonist Noggin, eFGF and Wnt-1-like proteins (8, 3a) exert a crucial function on lateral NC cell migration. All of these factors modulate migration and differentiation of NC cells when applied ectopically in other vertebrates such as zebrafish and chicken. We will first clone the cDNAs of these factors from the axolotl and study their embryonic expression pattern. We will then investigate their effect on lateral NC cell migration. We will implant protein-coated microbeads as well as Xenopus cells expressing BMP-4, Noggin, eFGF and Wnt-1-like proteins in the vicinity of the premigratory axolotl crest. Finally, the temporal analysis of gene function will be performed by heat shock-inducible expression constructs for BMP-4, Noggin eFGF and Wnts.

神经脊(NC)细胞的迁移是脊椎动物发育过程中的关键事件。墨西哥红豆杉(Ambystoma Micianum)的野生型(暗)和白色突变胚胎为研究NC细胞的横向迁移提供了独特的实验系统。在黑暗的胚胎中，NC来源的色素细胞在表皮下横向迁移。这种迁移在白色突变体中被抑制。这种缺陷的分子性质尚不清楚。本研究的目的是探讨转化生长因子β蛋白BMP-4及其拮抗剂Noggin、eFGF和WNT-1样蛋白(8，3a)是否在NC细胞横向迁移中发挥重要作用。当在斑马鱼和鸡等其他脊椎动物中异位应用时，所有这些因素都调节NC细胞的迁移和分化。我们将首先从Axolotl中克隆这些因子的cDNA，并研究它们的胚胎表达模式。然后，我们将研究它们对NC细胞横向迁移的影响。我们将在迁移前的轴突附近植入蛋白包裹的微球以及表达BMP-4、Noggin、eFGF和Wnt-1样蛋白的非洲爪哇细胞。最后，基因功能的时间分析将通过热休克诱导的BMP-4、Noggin eFGF和Wnts的表达构建来执行。