Collective Cell Migration and Chemotaxis
A mouse embryonic fibroblast migrating up a gradient of fibronectin (left, red arrow indicates higher concentration)
and the lamellipodia of a fibroblast stained for F-actin (red) and Arp2/3 (green) (Credit: Liz Haynes, Bear lab, UNC Chapel Hill)
and the lamellipodia of a fibroblast stained for F-actin (red) and Arp2/3 (green) (Credit: Liz Haynes, Bear lab, UNC Chapel Hill)
I spent my graduate schools days at UNC-Chapel Hill in the lab of James Bear studying the role of the actin cytoskeleton in directional cell migration (i.e. chemotaxis, haptotaxis). We used microfluidics chambers designed by Sreeja Asokan to form gradients of either extracellular matrix or soluble chemoattractants, then measured cells' ability to migrate efficiently on those gradients.
The zebrafish lateral line system is a wonderful example of collective cell migration and chemotaxis that has been well characterized by many groups. It is a sensory system allowing the zebrafish to sense local vibrations and currents in the water.
The posterior lateral line system (pLL) consists of a group of cells called the lateral line primordium (pLLp, pictured above), which is characterized by a CXCR4-expressing group of leader cells in front, and a CXCR7 positive group of trailing cells. The CXCR7 is a sink for the chemoattractant SDF-1/CXCL12, expressed along the horizontal myoseptum. CXCR7 binding and internalization of SDF-1 leads to the generation of a gradient of SDF-1 which is highest at the CXCR4-expressing leader cells. The axons of the pLL extend from the pLL ganglion just behind the otocyst to follow the primordium as it migrates. The primordium deposits groups of cells which will become neuromasts (as in L1, L2 above) along horizontal myoseptum, and these are innervated by the pLL axons.
The posterior lateral line system (pLL) consists of a group of cells called the lateral line primordium (pLLp, pictured above), which is characterized by a CXCR4-expressing group of leader cells in front, and a CXCR7 positive group of trailing cells. The CXCR7 is a sink for the chemoattractant SDF-1/CXCL12, expressed along the horizontal myoseptum. CXCR7 binding and internalization of SDF-1 leads to the generation of a gradient of SDF-1 which is highest at the CXCR4-expressing leader cells. The axons of the pLL extend from the pLL ganglion just behind the otocyst to follow the primordium as it migrates. The primordium deposits groups of cells which will become neuromasts (as in L1, L2 above) along horizontal myoseptum, and these are innervated by the pLL axons.
Pictured here is an example of the lateral line primordium and its trailing axons in a roughly 28HPF zebrafish embryo. The bullet shaped mass of cells in magenta is the primordium, while the axons are labeled in both magenta and green. (Credit: Liz Haynes, Halloran lab)