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Gene Expression During Embryonic Development Of Xenopus Laevis

$812,378Z01FY2008HDNIH

Eunice Kennedy Shriver National Institute Of Child Health & Human Development

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Abstract

This laboratory is studying the molecular basis of embryogenesis in Xenopus laevis. This project utilized DNA microarray technology for gene discovery in the early embryo, with the aim to obtain information on gene expression patterns in development and to lead to improved understanding of the molecular basis of normal embryogenesis. This approach allowed the identification of a protein in the family of guanine nucleotide exchange factors named WGEF that has a role in the Wnt-PCP pathway which regulates convergent extension movements in Xenopus. These cell movements are required in the establishment of body shape, and deficits in these movements can lead to malformations such a neural tube closure defects (NTDs). We have characterized the Rho-GEF we identified as a component of the Wnt-PCP signaling pathway that interacts with the known pathway components Dishevelled and Daam-1. The role and specific position of WGEF in the genetic hierarchy of the control of gastrulation movements has been determined.[unreadable] DNA microarray technology also led to the identification of a leucine-rich transmembrane protein named Lrig3 that we showed to be required for the formation of the neural crest. Experiments in the whole embryo and in explants induced to differentiate into neural crest have shown that the novel protein affects multiple signaling pathways in the embryo, in particular modulates the function of the Fibroblast Growth factor pathway. Epistasis experiments have been carried out to identify the position of the leucine-rich factor in the hierarchy of control of neural crest specification.

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