Contact with isolated sclerotome cells steers sensory growth cones by altering distinct elements of extension

Abstract

During pathfinding, growth cones respond to guidance cues by altering their motility. This study shows that motile responses can be highly specific: filopodial contact with two different, physiologically relevant cells differentially alters discrete elements of motility. With each cell type, the responses to contact are invariant. Each cell induces a distinct response in sensory growth cones with every filopodial contact. Contact with an inhibitory cell, posterior sclerotome, alters a discrete motile characteristic; contact locally inhibits the ability of veils to extend down contacting filopodia. The inhibition is precise. Contact fails to alter other individual veil characteristics such as initiation frequency or extension rate. Moreover, despite local veil inhibition, the general level of extension across the growth cone is retained, as though protrusive activity is regulated to some set point. Contact with a stimulatory cell, anterior sclerotome, elicits a biphasic response. First, contact stimulates extension generally, altering the set point of protrusion. Contact increases veils and filopodia throughout the growth cone persistently. Then contacting processes consolidate, forming neurite. Filopodia contacting either cell type have similar lifetimes but different fates. Filopodia contacting posterior cells show morphological indications of structural instability, likely related to their inability to support veil extension. Filopodia contacting anterior cells branch, become morphologically complex, and ultimately consolidate into neurite. The invariance and precision of these responses suggests they are the steering components elicited by contact. These steering components, when integrated with other motile events, modulate growth cone trajectory. The discreteness of these responses suggests that guidance cues affect equally discrete elements in signaling cascades.