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.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Neurology B Subcommittee 2 (NEUB)
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Henken, Deborah B
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California Institute of Technology
Schools of Arts and Sciences
United States
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Chen, Y; Gutmann, D H; Haipek, C A et al. (2004) Characterization of chicken Nf2/merlin indicates regulatory roles in cell proliferation and migration. Dev Dyn 229:541-54
Cerny, Robert; Meulemans, Daniel; Berger, Jurgen et al. (2004) Combined intrinsic and extrinsic influences pattern cranial neural crest migration and pharyngeal arch morphogenesis in axolotl. Dev Biol 266:252-69
De Bellard, Maria Elena; Rao, Yi; Bronner-Fraser, Marianne (2003) Dual function of Slit2 in repulsion and enhanced migration of trunk, but not vagal, neural crest cells. J Cell Biol 162:269-79
Peters, John; Sechrist, Jack; Luetolf, Simone et al. (2002) Spatial expression of the alternatively spliced EIIIB and EIIIA segments of fibronectin in the early chicken embryo. Cell Commun Adhes 9:221-38
De Bellard, Maria Elena; Ching, Wendy; Gossler, Achim et al. (2002) Disruption of segmental neural crest migration and ephrin expression in delta-1 null mice. Dev Biol 249:121-30
Kulesa, P; Bronner-Fraser, M; Fraser, S (2000) In ovo time-lapse analysis after dorsal neural tube ablation shows rerouting of chick hindbrain neural crest. Development 127:2843-52
Osterhaus, A D; Rimmelzwaan, G F; Martina, B E et al. (2000) Influenza B virus in seals. Science 288:1051-3
Garcia-Castro, M I; Vielmetter, E; Bronner-Fraser, M (2000) N-Cadherin, a cell adhesion molecule involved in establishment of embryonic left-right asymmetry. Science 288:1047-51
Kil, S H; Krull, C E; Cann, G et al. (1998) The alpha4 subunit of integrin is important for neural crest cell migration. Dev Biol 202:29-42
Saldivar, J R; Sechrist, J W; Krull, C E et al. (1997) Dorsal hindbrain ablation results in rerouting of neural crest migration and changes in gene expression, but normal hyoid development. Development 124:2729-39

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