EGFR Signaling Promotes Invadosome-Mediated 3-D Axon Outgrowth

Abstract

During development, axons and dendrites (collectively known as neurites) extend from neuron cell bodies to form appropriate synaptic connections, using secreted and cellsurface ligands as guides (Lowery & Vactor, 2009). The mediator of this outgrowth is the growth cone, a dynamic filamentous-actin (F-actin) rich end of neurites (Dent et al., 2011). Recently, our laboratory discovered that spinal neurons release matrix metalloproteinases (MMPs) at protrusive, F-actin foci known as invadosomes to overcome tissue barriers during development (Santiago-Medina et al., 2015; Short et al., 2016). Much remains unclear about the processes regulating growth cone invadosomes in vivo. Here, I hypothesize that epidermal growth factor (EGF) released from axial mesoderm acts through EGF receptor (EGFR) on motor neurons to stimulate growth cone invadosomal proteolytic activity.