RT Journal Article
SR Electronic
T1 Axon Sorting within the Spinal Cord Marginal Zone via Robo-Mediated Inhibition of N-Cadherin Controls Spinocerebellar Tract Formation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 15377
OP 15387
DO 10.1523/JNEUROSCI.2225-12.2012
VO 32
IS 44
A1 Nozomi Sakai
A1 Ryan Insolera
A1 Roy V. Sillitoe
A1 Song-Hai Shi
A1 Zaven Kaprielian
YR 2012
UL http://www.jneurosci.org/content/32/44/15377.abstract
AB 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.