Fig. 7. Model for integrin/Cas-mediated regulation of axonal fasciculation. (A) During axon pathfinding, integrin/Cas signaling (+) functions to regulate axon-axon fasciculation. In this model, integrin/Cas-mediated adhesive interactions are strongest at choice points, slowing axons so that they can navigate specific defasciculation events. (B) Removal of integrin or Cas adhesive signaling in a loss-of-function (LOF) mutant background prevents axons from defasciculating at their choice points, maintaining fasciculation with the main axon bundle. (C) Neuronal overexpression (gain-of-function, GOF) of Cas increases integrin/Cas adhesive signaling and also prevents axons from defasciculating at their choice points. This model suggests that integrin/Cas adhesive signaling is necessary for axonal defasciculation but is not sufficient, such that other guidance cues, including axonal repellents, coordinately work together with integrin/Cas signaling to direct specific axon defasciculation.