Everyone Gets to Drive
Authors: Gough Nancy R. 
Published: September 2007

During oogenesis in
Drosophila
, the border cells detach from the anterior side and migrate as a group of eight cells (six outer cells and two polar cells) toward the oocyte in the posterior, and then they turn and migrate dorsally toward the oocyte nucleus. Bianco
et al
. found that the cells use two different mechanisms to achieve this migration. It was known that two receptor tyrosine kinases--platelet-derived growth factor- and vascular endothelial growth factor-related receptor (PVR) and epidermal growth factor receptor (EGFR)--were involved in the process, with the two receptors functioning redundantly in the initial migratory phases and then EGFR taking over for the later phases. Bianco
et al
. investigated the downstream signaling events by creating loss-of-function mutants or mosaic animals in which only a subset of the cells were mutant. They found that a Rac, Mbc (myoblast city, also known as DOCK180, a Rac guanine nucleotide exchange factor), and the downstream effector ELMO (engulfment and cell motility, also known as Ced-12) were essential for the initial phase of posterior migration. ELMO-deficient cells arrested early in migration and failed to exhibit filamentous actin accumulation in response to constitutive PVR signaling. In mosaic border cells, during the initial posterior migration phase, ELMO-deficient cells were in the rear, which would be expected for cells that were not contributing to the migration process but were carried along by the wild-type cells, whereas ELMO-deficient cells were frequently in the leading position during dorsal migration. Screening for phosphotyrosine-binding proteins that interacted with the tyrosine in the EGFR that was critical for migration identified Shc, an adaptor that links receptor tyrosine kinases to mitogen-activated protein kinase (MAPK), phospholipase C-γ (PLC-γ), or phosphoinositide 3-kinase (PI3K) signaling. Border cells lacking functional Shc did not migrate dorsally. Double-mutant cells lacking both MAPK and PLC-γ signaling initiated migration but were delayed in reaching the posterior and did not migrate dorsally. Live-cell imaging of the border cells revealed that the movement occurred in two phases: a fast phase in which two highly polarized cells led the group, and a slower phase that occurred midway to the oocyte, during which the cells were round and the cluster tended to shuffle such that the leading cell changed approximately every 18 minutes. The early fast phase corresponds to the time when the Rac-Mbc-ELMO pathway is active, whereas the later phase corresponds to the time when MAPK and PLC-γ are important. Within individual cells, MAPK signaling was uniform; however, relative to other cells in the cluster, the cell with the highest MAPK signaling [phosphorylated extracellular signal-regulated protein kinase (ERK)] was located at the front of the cluster. With mosaic border cells, the authors showed that cells in which MAPK signaling was genetically increased tended to stay at or near the front. Thus, the authors suggest that, for the later phase of migration, the border cell cluster uses a "collective guidance" mechanism whereby each cell transmits guidance information to the entire cluster and the cells with the highest intensity of signaling compete for the front position, enabling forward movement.

A. Bianco, M. Poukkula, A. Cliffe, J. Mathieu, C. M. Luque, T. A. Fulga, P. Rørth, Two distinct modes of guidance signalling during collective migration of border cells.
Nature
448
, 362-365 (2007).
[PubMed]