Role of SynCAM1 in axon development of cranial somatic motor neurons

Abstract

Configuration of functional motor circuits that innervate muscles and control body movements is essential for our life. Many axon guidance and adhesion molecules are suggested to lead directional axon growth and axon-axon contact, either expressed in motor neurons or present in nearby populations that grow with motor axons. For instance, motor and sensory axons grow together in the periphery toward their targets, forming stable fasciculated axon bundles through contacts between motor and sensory neurons. However, it is unclear whether axon-axon interaction among motor nerves is also essential if motor nerves grow without sensory nerves, such as subsets of cranial nerves and some branches of cervical plexus in the neck. In this study, I showed that axon growth of hypoglossal, accessory, and motor components of cervical spinal nerve 1, 2 and 3, which together build elaborate purely-motor axon branches without assistance by sensory nerve, were severely disorganized when SynCAM1 was downregulated. This led to cell death and disrupted neuromuscular junction formation in their target muscles located in the tongue, neck, and shoulders. Consistent with their function in arm motion, SynCAM1 mutant mice showed problems in grip and coordinated movement related to forelimb. Together, motor nerves without sensory projection are more vulnerable to axon degeneration when axon-axon adhesion by SynCAM1 is compromised.