Professor Esther T Stoeckli, University of Zurich - To cross, or not to cross axon guidance mechanisms at choice points


During neural circuit formation, axons have to find their target cells to make appropriate synaptic contacts. Along their trajectory, axons contact one or several intermediate targets. At each of them, axons need to switch their behavior from attraction to repulsion in order to move on. Axon guidance at intermediate targets, or choice points, depends on the precise regulation of guidance receptors on the growth cone surface. Dorsal commissural (dI1) axons crossing the ventral midline of the spinal cord in the floor plate represent a convenient model for the analysis of the molecular mechanism underlying the switch in axonal behavior. We identified a role of morphogens, Shh and Wnt family members, along with members of the immunoglobulin superfamily of cell adhesion molecules, and class-6 semaphorins in commissural axon guidance at the floor plate. The multitude of guidance molecules required for axonal navigation at a seemingly easy decision point is surprising but also raises many more questions about the regulation of their expression on the growth cone surface at the time of midline navigation. In addition to regulation at the transcriptional level, we found a variety of post-translational mechanisms involved in the precise timing of guidance receptors. DPAG