In the trunk of the avian embryo, both neural crest cells and motor axons move through the rostral half of each somite, due to intrinsic differences within the somitic sclerotome. In the cranial region, neural crest cells move along defined pathways lined with extracellular matrix molecules. Recently, signaling pathways have been identified that can mediate morphological and behavioral changes in tissue culture cells. It is unclear, however, what role these pathways will play in the more complex movements involved in embryonic morphogenesis. The long-term goals of this proposal are to identify the cell interactions and intracellular signals that influence cell movement and localization in the neural crest system. The experimental design combines experimental manipulation of the environment by introduction of agents that block specific molecules or cell-cell and cell-matrix interactions with ectopic expression of molecules of interest by retrovirally-mediated gene transfer. The investigators will directly observe the effects of disrupting cell interactions on neural crest cell guidance by preparing trunk explants of living embryos in which neural crest cells are labeled with a membrane intercalating dye. The goal of the investigators is to identify interactions that are important in establishing the rostrocaudal polarity of the somites and the segmentation of the peripheral nervous system Using this accessible system, the investigators will look at the possible role of Eph receptors/ligands, integrins in the process of neural crest migration. To extend these studies from the cell surface to the intracellular domain, the investigators will analyze signal transduction pathways essential for neural crest migration. Candidate signaling pathways will be down-regulated by over-expressing dominant inhibitory mutants of known signal transducers, or up-regulated by over-expressing constitutively active mutants. Initial emphasis will be focused upon contributions by Rho-family GTPases.
The specific aims : 1. Characterize of molecules involved in the segmental migration of trunk neural crest cells. 2. Analyze of the role of integrins in cranial and trunk neural crest migration. 3. Analyze of the signal transduction pathways mediating neural crest migration.
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