Motor neuron migration and positioning mechanisms: New roles for guidance cues

Motor neurons differentiate from progenitor cells and cluster as motor nuclei, settling next to the floor plate in the brain stem and spinal cord. Although precise positioning of motor neurons is critical for their functional input and output, the molecular mechanisms that guide motor neurons to their proper positions remain poorly understood. Here, we review recent evidence of motor neuron positioning mechanisms, highlighting situations in which motor neuron cell bodies can migrate, and experiments that show that their migration is regulated by axon guidance cues. The view that emerges is that motor neurons are actively trapped or restricted in static positions, as the cells balance a push in the dorsal direction by repulsive Slit/Robo cues and a pull in the ventral direction by attractive Netrin-1/DCC cues. These new functions of guidance cues are necessary fine-tuning to set up patterns of motor neurons at their proper positions in the neural tube during embryogenesis.