Too much EGF receptor signaling increases P compartment size (left). Too little reduces it (right).

PARKER/ELSEVIER

Self reliance is not enough. Some organs rely on the kindness of others to control their size, according to Joseph Parker (Columbia University, New York, NY).

Correct organ size is measured in mass, not cell numbers—forcing or blocking cell division generally does not change an organ's overall dimensions. Parker found the same is true in the fly embryonic P compartment, which forms part of the larval epidermis. Increases in P compartment cell numbers were countered by more apoptosis and smaller cells. With fewer numbers, on the other hand, each cell grew larger to accommodate for their missing comrades.

In looking for a molecular explanation, Parker figured it would make sense to “have size information encoded right there in the patterning system” that also controls cell fate and positioning. For the P compartment, these patterning molecules are extracellular ligands called Spitz and Wingless. The new results show that more or less Spitz signaling creates larger and smaller P compartments, respectively.

At the individual cell level, Spitz suppressed apoptosis and encouraged cell growth by activating the EGF receptor and downstream MAP kinase pathways. To explain how overgrowth is prevented, Parker reasoned that “the simplest model is that the level of Spitz is fixed in the compartment. More proliferation means less Spitz per cell.” Those cells thus grow less and are more susceptible to apoptosis.

Organs were previously thought to have autonomous control over their size. But the new model only works if Spitz is provided by an external source—otherwise, a bigger P compartment would make more Spitz and grow even larger. Although Spitz is expressed everywhere, it is activated solely in the neighboring A compartment, from where it apparently diffuses into the P compartment.

Because ligands such as Spitz are short-range diffusers, the model probably only applies to small or embryonic structures in the range of tens to hundreds of cells. “For larger organs like the liver,” Parker says, “diffusion is a rickety thing” that might require backup size control mechanisms.

Reference:

Parker, J.
2006
.
Curr. Biol.
16
:
2058
–2065.