Gaining a better understanding of the mechanisms that govern normal cell motility and invasion is crucial for understanding development but may also contribute to understanding forms of aberrant cell invasion and migration of metastatic tumor

During the development of multicellular organisms, various types of directed cell migration occur that contribute to the development of different tissues. These include the migration of neural crest cells, hematopoietic stem cells and germ cells. Gaining a better understanding of the mechanisms that govern normal cell motility and invasion is crucial for understanding development but may also contribute to understanding forms of aberrant cell invasion and migration of metastatic tumor cells. Border cell migration during Drosophila oogenesis is one well-studied example of invasive and directed migration (Spradling, 1993; Montell, 2001; Rørth, 2002). Border cells are specified within the anterior follicular epithelium that surrounds the germ cells in each egg chamber (Fig. 1). At late egg chamber stage 8, approximately eight border cells delaminate from the monolayer epithelium and, in a highly stereotyped fashion, invade the germ cell cluster within the developing egg chamber (Montell et al., 1992; Niewiadomska et al., 1999). First, they undergo directed cell migration between nurse cells towards the anterior margin of the oocyte and then turn dorsally, coming to rest at the dorsal anterior corner of the egg chamber next to the underlying oocyte nucleus. Border cell migration displays several features that are reminiscent of metastasis by cancer cells (Thiery, 2002). Initially, border cells are polarized epithelial cells that loose some homophilic cell adhesion, undergo an epithelial-tomesenchymal transition, acquire adhesion with the substratum, and undergo cell migration. However, not all epithelial characteristics are lost during migration. The migrating cells remain attached to each other and intercellular polarized junctions containing DE-cadherin [also known as Shotgun (Shg)], Armadillo (Arm) and Crumbs are present (Peifer et al., 1993; Niewiadomska et al., 1999). DE-cadherin has been demonstrated to play an essential role in both migrating border cells, and their substratum, the germ cells (Oda et al., 1997; Niewiadomska et al., 1999). These previous studies suggest homophilic interactions between transmembrane receptors, such as DE-cadherin, may provide the necessary adhesion between invasive cells and their substratum. The Drosophila tumor suppressor genes discs large (dlg1 – FlyBase) and lethal (2) giant larvae (lgl; l(2)gl – FlyBase) play essential roles in epithelial cell polarity, adhesion and proliferation (Mechler et al., 1985; Jacob et al., 1987; Woods and Bryant, 1989; Woods and Bryant, 1991; Woods et al., 1996; Woods et al., 1997; De Lorenzo et al., 1999; Bilder et al., 2000). Follicle cell epithelia mutant for dlg undergo an epithelial-to-mesenchymal transition driving their invasion between germ cells, in a pattern similar to that observed in migrating border cell clusters (Goode and Perrimon, 1997). Within follicle cells, Dlg localizes to the basolateral membrane and, in germ cells, the protein is present at sites of contact 1927 Development 130, 1927-1935 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00420