Abstract
During brain development, guidance cues instruct migrating neurons to orient their growth as they navigate through the extracellular milieu. The spatial and temporal organization of these guidance cues is crucial for proper brain assembly. One evolutionarily conserved guidance cue for the development of nervous systems is netrin. Receptors that neurons use to receive netrin signals, as well as the intracellular transduction machinery that reorganizes the cytoskeleton to direct the migrating growth cone have been elucidated. However, how netrin itself is distributed extracellularly and how the interactions between netrin and its receptors are modulated for neurons to be correctly guided is unknown.
Taking genetic, molecular and biochemical approaches, we have investigated what molecules might be regulating netrin signals during the development of the nervous system of the model organism C. elegans. We have identified of a proteoglycan that functions as a regulator of netrin‐guided migrations. We show that the glycan chains themselves are important for this proteoglycan function in netrin guidance. We also show that a second proteoglycan, modulates the signalling of another complementary guidance cue, slit. Thus two proteoglycans play complementary roles in modulating the guidance by two paired guidance cues.