Injured Axons Instruct Schwann Cells to Build Constricting Actin Spheres to Accelerate Axonal Disintegration

Abstract

Summary: After a peripheral nerve lesion, distal ends of injured axons disintegrate into small fragments that are subsequently cleared by Schwann cells and later by macrophages. Axonal debris clearing is an early step of the repair process that facilitates regeneration. We show here that Schwann cells promote distal cut axon disintegration for timely clearing. By combining cell-based and in vivo models of nerve lesion with mouse genetics, we show that this mechanism is induced by distal cut axons, which signal to Schwann cells through PlGF mediating the activation and upregulation of VEGFR1 in Schwann cells. In turn, VEGFR1 activates Pak1, leading to the formation of constricting actomyosin spheres along unfragmented distal cut axons to mediate their disintegration. Interestingly, oligodendrocytes can acquire a similar behavior as Schwann cells by enforced expression of VEGFR1. These results thus identify controllable molecular cues of a neuron-glia crosstalk essential for timely clearing of damaged axons. : Vaquié et al. demonstrate that injured axons signal to Schwann cells to induce the formation of actin spheres, which constrict axons until their disintegration, thereby accelerating the clearing of axonal debris after lesion. This behavior, controlled by VEGFR1 activation, can be acquired by oligodendrocytes through enforced expression of VEGFR1. Keywords: Schwann cells, oligodendrocytes, axonal injury, myelinated models, axonal disintegration, PlGF, VEGFR1, Pak1, constricting actomyosin spheres