The brake within: Mechanisms of intrinsic regulation of axon growth featuring the Cdh1-APC pathway

Abstract

Neurons of the central nervous system (CNS) form a magnificent network destined to control bodily functions and human behavior for a lifetime. During development of the CNS, neurons extend axons that establish connections to other neurons. Axon growth is guided by extrinsic cues and guidance molecules. In addition to environmental signals, intrinsic programs including transcription and the ubiquitin proteasome system (UPS) have been implicated in axon growth regulation. Over the past few years it has become evident that the E3 ubiquitin ligase Cdh1-APC together with its associated pathway plays a central role in axon growth suppression. By elucidating the intricate interplay of extrinsic and intrinsic mechanisms, we can enhance our understanding of why axonal regeneration in the CNS fails and obtain further insight into how to stimulate successful regeneration after injury.