From sports huddles to sewing circles, groups congregate to exchange confidences within a restricted group. Cells, too, appear to communicate this way, confining signaling molecules among a select few in-the-know participants.

This cellular communications mode has been discovered only recently, and evidence for it is limited to cells of developing zebrafish. Still, it could be far more widespread. It could, for example, influence processes such as wound repair, organ formation, and even cancer.

Evidence that cells can organize to communicate more intensively within a select group has been collected by scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. These scientists investigated how the process of tissue assembly controls signaling activity during organogenesis in vivo, using the migrating zebrafish lateral line primordium. The lateral line consists of a series of ear-like organs along the fish’s flank that allow it to sense changes in water pressure.

As a zebrafish develops, a mass of cells moves along the developing animal’s side. At the point where one of these organs should form, a group of cells at the rear assembles into a huddle and stops, eventually developing into the organ. The rest of the cells, meanwhile, have moved on, until another group stops to form another organ, and so on.

The cells that group together and stop to form the future organ also change shape, going from flat, crawling cells to upright, tear-shaped cells that come together like cloves in a bulb of garlic. The cells, by forming this garlic-clove-shaped huddle, enclose a shared space, or lumen, that serves to trap fibroblast growth factor (FGF).

These findings appeared October 22 in Nature, in an article entitled, “Luminal signalling links cell communication to tissue architecture during organogenesis.”

“We show that FGF activity within the tissue controls the frequency at which it deposits rosette-like mechanosensory organs,” wrote the authors. “Live imaging reveals that FGF becomes specifically concentrated in microluminal structures that assemble at the center of these organs and spatially constrain its signaling activity.”

The curious thing is that concentrations of FGF seem to correlate with behaviors of lateral-line cells.
“Normally, FGF acts as a long-range communication signal. In the lateral line, we find that most of this signal is normally just wafting over the cells’ heads,” said EMBL’s Darren Gilmour, Ph.D. “But when cells get together and huddle they can trap and concentrate this signal in their shared lumen, and make a decision that the others can’t: they stop moving.”

When the scientists increased the concentration of FGF, cell huddles came to a standstill more abruptly, forming organs that were closer together. And when the scientists decreased the level of FGF, huddles continued to migrate for longer and formed organs that were further apart.

In the Nature article, the authors noted that studies of extracellular signaling have tended to focus on the regulatory potential of additional cell surface or extracellular proteins. Alongside such mechanisms, which are currently under investigation, the authors propose an alternative—a mechanism that exploits an intrinsic biological feature of epithelial tissues, namely their ability to assemble a shared enclosed lumen.

“To our knowledge, [the mechanism we describe] provides the first such mechanism that acts specifically at the level of multicellular organization, as only cell groups that assemble a central lumen are able to trap and concentrate the freely diffusible ligand,” the authors asserted. “Moreover, as lumen formation itself is highly sensitive to changes in epithelial polarity and adhesion, it is likely that luminal signaling hubs can be rapidly disassembled and reassembled by processes that alter cell cohesion, such as the epithelial–mesenchymal transition that is a hallmark of organogenesis and cancer.”

The authors also noted that the formation of a central lumen is a self-organizing property of many cell types, such as epithelia and embryonic stem cells. This observation suggests that luminal signaling could be fairly common, a widely used means of locally restricting, coordinating, and enhancing cell communications within tissues. Ultimately, the authors concluded that their study “suggests potential signaling roles for shared lumina in many other tissue contexts.”








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