Migration and shape of a Cxcr4b-deficient cell mass (green) is rescued by a clone of WT cells (red).

GILMOUR

Organogenesis requires the collective movement of large groups of cells during development. According to a new study by Petra Haas and Darren Gilmour (European Molecular Biology Laboratory, Heidelberg, Germany), one such mass transit is directed by a few leader cells that respond to a chemokine signal to guide the trek and keep the marching troops in formation.

The cluster of about 100 cells that forms the posterior lateral line primordium (pLLP), the progenitor of the zebrafish mechanosensory organ, marches down a stripe of the stroma-derived factor 1 (SDF1) chemokine. Time-lapse imaging showed that the tissue's trajectory was controlled by cells that extended filopodia on the leading outer edge of the pLLP. For the column of cells to move, only leader cells required Cxcr4b, the SDF1 receptor; cells on the interior of the pLLP did not need the receptor.

Leaders in pLLP migration seem to get appointed to the post, perhaps by having higher receptor activity, says Gilmour. When wild-type and Cxcr4b-lacking cells were combined in genetic mosaic experiments, the wild-type cells quickly took position on the leading edge to restore proper movement.

“We think the job of guiding will be given to those cells that initially sense the most,” Gilmour says. “The cluster is extremely unstable. Whenever it has reduced chemokine signaling, it rolls around, and it is this instability that allows sensing cells to get into a position where they can reinstate order.” As few as four transplanted Cxcr4b-expressing cells were able to curb the chaos and generate normal movement in mutant tissue.

Solo cell migration is known to be regulated by diffusible gradients of chemokines, but guidance of the pLPP relies more on the self-organization of the cell mass. In mutants with spatially interrupted SDF1 expression, the pLLP made a U-turn where SDF1 ended and reentered the chemokine stripe from the reverse direction. A U-turn would be unlikely in a gradient-controlled situation.

How leader cells coordinate movement is not yet known. One possibility is mechanical pushing and pulling forces among cells. Gilmour believes that the mechanism may apply generally to the migration of cell groups.

Reference:

Haas, P., and D. Gilmour.
2006
.
Dev. Cell.
10
:
673
–680.