Deciphering the axon growth mechanism of regenerating sensory neurons

Barbara Schaffran1, Frank Bradke1

1 German Center for Neurodegenerative Diseases, Bonn, Germany

Axons in the central nervous system (CNS) do not regenerate after injury.  However, during development neurons polarize and rapidly extend their axon finding appropriate targets. This is driven by the growth cone, the highly motile structure, at the tip of the axon which includes all necessary machinery.  Actin and microtubules are major components of the growth cone and have been shown to play important roles in axon extension.  To date it is not clear, what the driving forces in CNS and peripheral nervous system (PNS) axon extension are and which mechanisms are important for axon regeneration.
Previous results from our lab show that developing CNS neurons extend their axons independent of adhesions to the extracellular matrix, suggesting an amoeboid type of movement.  In this case axon growth is driven by microtubule polymerization.
Here we analyse growth mechanisms of DRG sensory neurons. By manipulating the actin cytoskeleton, we show, that DRG neurons grow in a fundamentally different way to developing CNS neurons.  DRG neurons, in contrast to CNS neurons, do not grow, when actin polymerization is blocked.  Using a three-dimensional culture system and video-microscopy we identify forces and the need of adhesions of growing sensory neurons.  Future experiments will elucidate the important players in sensory axon extension and how this could implicate axon regeneration after injury.