University of Cambridge > Talks.cam > Genetics Seminar  > Studying the invasive migration of Drosophila immune cells.

Studying the invasive migration of Drosophila immune cells.

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Host: Boris Adryan

Both metastatic cancer cells and immune cells pursuing infections must penetrate the adherens junctions present in the endothelial barrier of the blood vessel wall to reach tissues. This transmigration requires the Rap1 GTPase to modulate Integrin affinity. We have defined a step in the developmental migration of Drosophila macrophages that we believe can serve as a model system to dissect the genetic pathways that control such transmigration. Using live imaging and genetics, we have discovered that Drosophila melanogaster immune cells penetrate an epithelial, DE-Cadherin-based tissue barrier during their embryonic developmental movements into the tail. A mutant in RhoL, a GTPase homolog that is only expressed in Drosophila macrophages at this stage, specifically blocks this invasive step but not other aspects of guided migration. The invasion defect in rhoL mutants can be rescued by lowering embryonic DE-Cadherin levels, arguing that RhoL is required to allow hemocytes to penetrate adherens junctions. We also show that RhoL is localized to the cell surface and mediates Integrin adhesion in hemocytes. We observe that RhoL mutants fail to transport the Integrin activator Rap1 from a cytoplasmic concentration to the leading edge during invasion. We have identified many mutants in genes expressed in hemocytes with defects in movement into the tail, two of which have been linked to metastasis in mice. My lab is utilizing these mutants to try to shed new light on the process of invasive migration, and will try to translate these findings into vertebrate systems. I will discuss our latest findings on a few of them.

This talk is part of the Genetics Seminar series.

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