Lateral line primordium with reduced Cxcr7 activity (Cxcr7Mo, green) exhibiting rescued forward migration in the presence of a small number of transplanted wild-type cells (red) in trailing regions.

Image courtesy of Dr. Darren Gilmour, European Molecular Biology Laboratory, Heidelberg, Germany.

Cells must migrate to the areas where they are needed during organ system morphogenesis. These cells commonly move as adherent groups or tissues rather than as single units, but the way in which this is coordinated within the migrating tissue remains elusive. In Current Biology, Gilmour and colleagues now report that two independent receptors respond to the same extracellular signal to drive migration at the front and rear of the lateral line primordium.

The lateral line is comprised of mechanosensory hair organs (neuromasts), which are typically present on the body surface and allow both fish and amphibians to perceive movement in the surrounding water — a must-have for survival. During development, these neuromasts are deposited at regular intervals along a pathway extending from head to tail via the collective migration of over one hundred primordial cells. Previous work by the same group showed that cells at the leading edge require chemokine receptor Cxcr4b activity in addition to the chemoattractant stromal-derived factor 1a (SDF1a) to guide the cohesive cohorts.

So how do the trailing cells keep up? Gilmour and colleagues now report that these cells also have a second chemokine receptor that allows cells at the very back of the grouptorespond to SDF1a, thus enabling them to stick with the crowd. The authors isolated an SDF1a loss-of-function zebrafish mutant (medusa) that exhibited defects in primordium migration and formed far fewer neuromasts, if any at all. The medusa phenotype was stronger than that of Cxcr4b-null mutants, prompting the authors to search for additional receptors.

Gilmour and colleagues identified the zebrafish homologue of another SDF1-binding receptor, Cxcr7, as being important. Cxcr7 expression was restricted to cells in the trailing part of the migrating primordium, unlike Cxcr4b, which is expressed more highly in cells in leading regions. Time-lapse imaging of cxcr7 morphant embryos revealed that, while cells at the front of the primordium extended normally, cells at the rear were uncoordinated and sent protrusions in all directions. This difference in migration behaviour causes the tissue to stretch and often split. Inactivation of both Cxcr4b and Cxcr7 showed additive phenotypes that were similar in strength to those observed in SDF1a mutants.

Gilmour and colleagues used rescue studies to confirm that Cxcr7 acts specifically at the rear through rescue studies. When transplanted into cxcr7 morphant embryos, wild-type cells rescued migration defects only when they were placed among trailing cells. Together, these results indicate that Cxcr4b and Cxcr7 ensure coordinated migration by mediating SDF1a signalling in spatially distinct domains of the same tissue.

These studies open the intriguing question of why it is important to have different receptors that respond to the same guidance cue. Does SDF1a trigger qualitatively different responses when binding to either Cxcr7 or Cxcr4b? Signalling studies from other cell systems suggest this may be the case. Cells at the front and rear of the primordium differ in their migration properties, so one possibility is that these distinct receptors may allow autonomous behaviours while ensuring coordinated movement.

Author: Kim Baumann