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

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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.