Axon sorting within the spinal cord marginal zone via Robo-mediated inhibition of N-cadherin controls spinocerebellar tract formation.

The axons of spinal projection neurons transmit sensory information to the brain by ascending within highly organized longitudinal tracts. However, the molecular mechanisms that control the sorting of these axons within the spinal cord and their directed growth to poorly defined targets are not understood. Here, we show that an interplay between Robo and the cell adhesion molecule, N-cadherin, sorts spinal commissural axons into appropriate longitudinal tracts within the spinal cord, and thereby facilitates their brain targeting. Specifically, we show that d1 and d2 spinal commissural axons join the lateral funiculus within the spinal cord and target the cerebellum in chick embryos, and that these axons contribute to the spinocerebellar projection in transgenic reporter mice. Disabling Robo signaling or overexpressing N-cadherin on these axons prevents the formation of the lateral funiculus and the spinocerebellar tract, and simultaneously perturbing Robo and N-cadherin function rescues both phenotypes in chick embryos. Consistent with these observations, disabling Robo function in conditional N-cadherin knock-out mice results in a wild-type-like lateral funiculus. Together, these findings suggest that spinal projection axons must be sorted into distinct longitudinal tracts within the spinal cord proper to project to their brain targets.

Are paragriseal cells in the avian lumbosacral spinal cord displaced ventral spinocerebellar tract neurons?

In lumbosacral segments the spinal cord of birds contains numerous paragriseal neurons lying in the white matter of lateral and ventral funiculus. These paragriseal cells project to the cerebellum. Neurons of the dorsal horn (mainly Clarke's column) make up a dorsal spinocerebellar tract and neurons of the ventral horn (mainly spinal border cells) are at the origin of a ventral spinocerebellar tract. It was the aim of this investigation to look for the distribution of spinocerebellar ventral horn neurons and paragriseal cells in the thoracolumbosacral spinal cord of pigeons and to compare this distribution with that of the cervical enlargement. Neuroanatomical tracers were injected into the anterior cerebellum of pigeons and labeled spinal neurons were counted throughout the length of the spinal cord. In the cervical enlargement the number of spinocerebellar ventral horn neurons increases more rostral than that of dorsal horn neurons but the number of both groups of neurons decreases simultaneously at the caudal end of the enlargement. In the ventral horn of thoracolumbosacral segments the number of spinocerebellar ventral horn neurons and paragriseal cells increases again more rostrally than that of dorsal horn cells. However, the number of ventral horn cells decreases whereas that of paragriseal cells and of dorsal horn cells is maintained. This shows that the number of ventral horn cells decreases in favor of paragriseal cells, which supports the suggestion that paragriseal cells are displaced ventral horn spinocerebellar neurons. It is discussed whether the paragriseal neurons migrate toward their input.