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

Abstract

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.

Slit/Robo signals prevent spinal motor neuron emigration by organizing the spinal cord basement membrane

“…It is interesting to note that the floor plate function was not necessary to retain motor neurons in the spinal cord. Contrast to the previous reports showing a ventral repulsive role in controlling the position of the motor neurons within the neural tube, prevention attraction into the floor plate (Kim et al, 2017a;Kim et al, 2015), and in setting the position of the motor exit point (Kim et al, 2017b), emigration does not neatly fit into a push-pull balance between midline attraction and repulsion. The results instead point to a local role in controlling the ability of motor neurons to either stay in their normal place in the nucleus, or emigrate out.…”

TAG-1 Multifunctionality Coordinates Neuronal Migration, Axon Guidance, and Fasciculation

“…To reach their final destinations, motor axons avoid inappropriate targets along the way. Multiple studies indicate that motor axons need to be actively prevented from projecting into DRGs after exiting the spinal cord, as subsets of motor axons invade DRGs in EphA3/4 double knockouts, EfnB1 À/À mice, CNS-specific FGFR1 knockouts, and Robo1/2 double mutants (Gallarda et al, 2008;Kim et al, 2019;Luxey et al, 2013;Shirasaki et al, 2006). Additionally, overexpression of Sema3A in MNs causes motor axon misprojection into DRGs (Moret et al, 2007).…”

Multifaceted roles of microRNAs: From motor neuron generation in embryos to degeneration in spinal muscular atrophy

“…Interestingly, miR-218 is encoded by an intron of the extracellular matrix Slit2 and Slit3 genes and it inhibits expression of neural cell adhesion molecules Robo1 and Robo2 and multiple components of the heparan sulfate biosynthetic pathway responsible for normal vascularization of the retina (Small et al, 2010). Given that recent evidence indicates that the function of the Slit-Robo regulatory axis is also important for proper positioning of MNs and their exit points (Kim et al, 2019), it would be interesting to investigate if the miR-218 -Slit-Robo autoregulatory loop is also important for MN axon pathfinding and targeting (Figure 3D).…”