Prof Daria Siekhaus

The breaching of tissue barriers underlies important developmental and physiological processes such as microglia formation, immune responses and cancer metastasis. Yet it is a relatively understudied aspect of migration. My lab has identified a new model system to study this process, macrophage infiltration of tissues in the Drosophila embryo, and is using it to identify new molecular pathways and cell biological principles involved in tissue invasion. In this seminar I will synthesize our published and unpublished work. I will show that tissue invasion requires changes in the tension and division of the surrounding tissues and in the state of the macrophages themselves. The decreased tension in the surroundings is triggered by the Drosophila ortholog of the vertebrate inflammatory cytokine TNF. Simultaneously inside the macrophages specific transcriptional, post transcriptional and translational changes have been initiated to facilitate their entry and movement within the tissue. This occurs both by the action of Drosophila orthologs of components previously linked to cancer such as fos and BMP and novel players we have identified which affect the ECM secretion and metabolic capacities of the invading macrophages. The vertebrate orthologs of these novel players have conserved functions, arguing that our system allows us to achieve insights into general mechanisms of tissue invasion that we hope in the long run will improve the treatment of autoimmunity and cancer.