Abl signaling shapes the intrinsic fluctuations of actin to direct growth of a pioneer axon in Drosophila

Abstract

33The fundamental problem in axon growth and guidance is to understand how cytoplasmic signaling 34 modulates the cytoskeleton to produce directed growth cone motility. We show here that the TSM1 35 pioneer axon of Drosophila extends by using Abl tyrosine kinase to shape the intrinsic fluctuations 36 of a mass of accumulated actin in the distal axon. The actin mass fluctuates stochastically in length, 37 but with a small, forward bias that drives the axon along its trajectory by promoting emergence of 38 protrusions in leading intervals where actin accumulates, and collapse of protrusions in lagging 39 intervals that actin has vacated. The actin mass is sculpted by Abl signaling, which 40 probabilistically modulates its key parameters -its width and internal disorder -to drive its 41 advance, while maintaining internal coherence. Comparison of TSM1 to other systems suggests 42 that the mechanism we demonstrate here is apt to be common among pioneer axons in many 43 organisms. 44 45 46