Bespalov et al. catch several growth factors that are essential for brain development being unfaithful. The researchers show that the molecules consort with a second receptor.

Glial cell line–derived neurotrophic factor (GDNF) and three related growth factors make up the GDNF family ligands, or GFLs. The molecules are movers and shapers in the nervous system. GFLs nurture neurons, trigger their neurites to grow, and prod the cells to migrate as the brain develops. Previous work identified GFR-α as the GFL co-receptor. GFR-α relays the signal to either of two other membrane receptors, RET or NCAM. However, researchers have found that some neurons can respond to GDNF even though they lack RET and NCAM, suggesting the GFLs can switch to a different receptor.

Their other partner, Bespalov et al. discovered, is syndecan-3, a heparan sulfate proteoglycan. Which receptor GFLs use depends on the situation, the team found. Free-floating GFLs hook up with GFR-α. But the growth factors often build up on the extracellular matrix (ECM), boosting their local concentrations. When attached to the ECM, three of the four GFLs send messages through syndecan-3.

In the embryo, GABAergic neurons, which are key inhibitory cells, travel from their birthplace in the medial ganglionic eminence into the brain cortex. To determine whether GFLs spur this behavior through syndecan-3, the researchers set beads that exude GDNF atop slices of rat brain. GABAergic neurons slithered toward the beads in slices from control animals, but not in tissue from animals lacking syndecan-3. The interaction between GFLs and syndecan-3 might therefore be critical for shaping the developing brain.

et al
J. Cell Biol.