Motility Determinants in Drosophila

The transition of a cell from a sessile to a migratory phenotype is a feature shared by normal cells during development and abnormal cells during metastasis. Much interest thus centers on the program of gene expression required for cell migration. Border cells in Drosophila undergo invasive migration during a defined window in oogenesis and represent a model system for the analysis of cell migration in vivo. In background studies, we have shown that RNAi is effective in the down regulation of gene products already known to be required for border cell migration from mutation analysis. It is therefore proposed to use the unique RNAi fly library developed by Dr Barry Dickson at IMBA/IMP to screen for genes required for migration, utilizing border cell invasion as an in vivo migration model. Secondary screens, of cell migration during thorax closure and lateral neuron outgrowth in Drosophila, will be used to establish candidate genes serving a general role in migration. Emphasis will be placed on those genes with homologues in higher vertebrates and the effects of those genes on cell migration will be analysed in mouse melanoma cells. The findings from these studies are expected to throw new light on the networks of genes involved in cell migration and invasion.

The transition of a cell from a sessile to a migratory phenotype is a feature shared by normal cells during development and abnormal cells during metastasis. Much interest thus centers on the program of gene expression required for cell migration. Border cells in Drosophila undergo invasive migration during a defined window in oogenesis and represent a model system for the analysis of cell migration in vivo. In background studies, we have shown that RNAi is effective in the down regulation of gene products already known to be required for border cell migration from mutation analysis. It is therefore proposed to use the unique RNAi fly library developed by Dr Barry Dickson at IMBA/IMP to screen for genes required for migration, utilizing border cell invasion as an in vivo migration model. Secondary screens, of cell migration during thorax closure and lateral neuron outgrowth in Drosophila, will be used to establish candidate genes serving a general role in migration. Emphasis will be placed on those genes with homologues in higher vertebrates and the effects of those genes on cell migration will be analysed in mouse melanoma cells. The findings from these studies are expected to throw new light on the networks of genes involved in cell migration and invasion.