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Axonal path finding of the accessory nerve

Subject Area Developmental Neurobiology
Developmental Biology
Term from 2018 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 404081011
 
Final Report Year 2024

Final Report Abstract

The accessory nerve is formed by a cranial and a spinal radix, which are also referred to as the internal and external ramus in the English literature. The latter is more commonly referred to as the spinal accessory nerve (SAN), as its axons exit the cervical spinal cord laterally and ascend cranially along the spinal cord into the cranial cavity. Then, the SAN turns laterally and exits the skull through the jugular foramen to innervate the muscles of the superficial neck and back. During embryonic development of the SAN, two growth phases may be distinguished: (1) Initially, axons of the SAN run longitudinally along the cervical neural tube, the embryonic precursor structure of the cervical spinal cord, and (2) then they switch and turn laterally, taking a transverse direction, and pass through the first somite which forms the jugular foramen. In this project, our goal was to investigate these two phases of axonal growth and their transition. Our data show that after the removal of NCCs at the level of the cervical neural tube, SAN- axons deviate from their longitudinal trajectory. Removal of sensory ganglia results in the absence of transverse SAN-axons at the level of the first somite, while heterotopically transplanted ganglia divert SAN-axons to exit at different locations. Inhibition of Neuropilin, and Plexin gene expression in SAN neurons by electroporation of shRNA constructs leads to defasciculation and deviation of SAN-axons from their normal route. Moreover, co-culture experiments demonstrate that sensory ganglia promote the outgrowth of motor axons through neurotrophic factors such as Brain-Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF). Conversely, the axonal outgrowth of sensory ganglia is stimulated by FGF8 from the pharyngeal arch. Based on the results of this project, we can outline a model of SAN-axon pathfinding. Neural crest cells act as boundary keepers and form a tunnel alongside the neural tube. SAN-axons are restricted to projecting exclusively within this tunnel. The Semaphorin/Neuropilin/Plexin signalling system mediates the interaction between SAN-axons and neural crest cells. It remains unclear why they project only cranially. At the level of the first somite, SAN-axons are guided out of the tunnel by sensory ganglia. Sensory axons might serve as guide rails for SAN-axons.

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