Gene Expression During Embryonic Development Of Xenopus Laevis

Child Health And 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 (GEFs) 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. In a related project the role of profilin in convergent extension was investigated. Profilin was shown to be an effector of Daam-1 in the regulation of cytoskeletal changes in response to Wnt-PCP signaling in the Xenopus embryo. Loss of function of profilin in the embryos leads to a neural tube closure defect in the posterior region of the embryonic axis.[unreadable] The application of DNA microarray technology further led to the identification of a novel transcription factor named Myoskeletin (MyoS) that has a role in the formation of muscle. MyoS is expressed in the somites and the hypaxial muscles of the Xenopus embryo, and is capable of activating the expression of several muscle-specific genes. Reduced function of MyoS in the embryo leads to a reduction in the formation of hypaxial muscles, the precursors of ventral body musculature. Thus MyoS is an essential component in the normal development of the embryo.[unreadable] DNA microarray technology also led to the identification of a leucine-rich transmembrane protein 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. Epistasis experiments have been carried out to identify the position of the leucine-rich factor in the hierarchy of control of neural crest specification.