In mammals, signals transmitted from the central nervous system (CNS) to muscles via motoneurons control movement. To form these circuits, motoneurons extend their axons out of the CNS at specialised exit points. Here (), Zaven Kaprielian and colleagues use mouse spinal accessory motoneurons (SACMNs) to investigate how this essential phase of motor axon pathfinding is controlled. SACMNs, which innervate neck and back muscles, leave the spinal cord at lateral exit points (LEPs). In mice lacking the homeodomain transcription factor Nkx2.9, the researchers report, SACMN axons project normally to the LEP but fail to exit the CNS. Robo2 expression in SACMNs is downregulated in Nkx2.9 null mice, they report, and SACMN axons fail to exit the spinal cord in Robo2-deficient animals. Finally, the Robo2 ligands Slit1-3 are present at the LEP and SACMN axons fail to exit the CNS in Slit-deficient mice. Together, these results suggest that Nkx2.9 controls SACMN axon exit from the CNS by regulating Robo2-Slit signalling.
