Pernille Rørth received her PhD from University of Copenhagen, Denmark, studying transcriptional regulation. The PhD work was done at the Carnegie Institute of Washington, Department of Embryology and was followed by a staff associate position the same place, working on Drosophila genetics (including developing the EP screen). From 1998, Pernille has been studying cell migration in Drosophila, first at European Molecular Biology Laboratory (EMBL) as a group leader and senior scientist, and from 2007 as senior PI at TLL in Singapore. Pernille joined IMCB as Research Director in July 2009.

Developmentally controlled cell migration can occur either as single cell migration or as group migration. Migration of individual cells has been extensively studied, but we know much less about the regulatory mechanisms controlling group, or collective, migration. Recent findings that invasive movement of tumor cells, in particular those derived from squamous carcinomas, often occurs as collective migration underscores the importance of understanding this type of migratory behavior. Border cells, a cluster of about 8 cells, perform a spatially and temporally controlled collective migration during Drosophila oogenesis. These cells first delaminate from an epithelium, then invade the underlying germ line tissue and perform a directional migration (to the oocyte). The lab uses border cell migration as a model system to investigate how cells become migratory and how cell and cluster movements are controlled and guided in vivo. This model system combines the advantages of a genetically tractable in vivo system (Drosophila) with the ability to image the migration live as shown below.

Previous work in the lab has shown that border cells find their way to the oocyte by using two receptor tyrosine kinases (RTKs), EGFR and PVR (PDGF/VEGF Receptor), as guidance receptors. Ligands for both are produced by the oocyte. We have evidence that the cell cluster uses two fundamentally different types of guidance signaling. One depends on correct spatial localization of RTK signaling within each of the migrating cells as in single-cell migrations. In the second mode, the border cell cluster processes guidance information as a collective. Other studies from the lab have shown that RTK endocytosis helps shape signaling in space, that mechanical forces may help control robustness of invasive cells through the MAL/SRF transcription factor and provided insight into how the cell-cell adhesion molecule DE-Cadherin is used for dynamic cell-on-cell migration (see publications). The lab is now further investigating the cell behaviors that lead to net directed migration of the border cell group and how is this controlled by guidance cues. We are particularly interested in understanding features reflecting the collective nature of this migration. To approach this, we are combining genetic manipulations with detailed quantitative analysis of morphogenetic traits, for the individual cells as well as for the cell group. The projects in the lab explore the following areas: (a) The signaling pathways that affect the cell behaviors and their interactions (including the role of endocytosis) (b) The adhesion between the migrating cells and their (cellular) substratum and its regulation, and (c) The cytoskeleton, its regulation with possible links to mechanobiology. Finally, we are studying how the border cells become migratory and initiate their invasive migration.