Ryk-mediated Wnt repulsion regulates posterior-directed growth of corticospinal tract

Abstract

Guidance cues along the longitudinal axis of the CNS are poorly understood. Wnt proteins attract ascending somatosensory axons to project from the spinal cord to the brain. Here we show that Wnt proteins repel corticospinal tract (CST) axons in the opposite direction. Several Wnt genes were found to be expressed in the mouse spinal cord gray matter, cupping the dorsal funiculus, in an anterior-to-posterior decreasing gradient along the cervical and thoracic cord. Wnts repelled CST axons in collagen gel assays through a conserved high-affinity receptor, Ryk, which is expressed in CST axons. Neonatal spinal cord secretes diffusible repellent(s) in an anterior-posterior graded fashion, with anterior cord being stronger, and the repulsive activity was blocked by antibodies to Ryk (anti-Ryk). Intrathecal injection of anti-Ryk blocked the posterior growth of CST axons. Therefore, Wnt proteins may have a general role in anterior-posterior guidance of multiple classes of axons.

Daam1 regulates the endocytosis of EphB during the convergent extension of the zebrafish notochord

“…In axonal pathfinding, EphBs and Wnts have been identified as guidance molecules for spinal cord commissural axons and corticospinal axons (24,25). Recently, Wnt3, a classical morphogen, has been identified as a guidance factor, counterbalancing EphB/EphrinB1 activity (26).…”

Activity- and use-dependent plasticity of the developing corticospinal system☆

“…Work in rodents has examined differentiation of CS neurons Molyneaux et al 2005) and guidance of their axons to the spinal cord (Terashima, 1995;Dottori et al 1998;Joosten and Bar, 1999;Coonan et al 2001;Liu et al 2005). Evidence shows that these processes are driven by transcriptional codes and intrinsic factors in the developing nervous system.…”

“…The role activity-independent processes in development of the CS projection to the spinal cord is only beginning to be understood (Dottori et al 1998;Joosten and Bar, 1999;Coonan et al 2001;Liu et al 2005). After CS axon terminals contact their spinal (and brain stem) targets, activity-dependent processes are key to refining connections and establishing the mature pattern of topographic and connectional specificity.…”

Wnt signaling establishes anteroposterior neuronal polarity and requires retromer inC. elegans

“…Wnts signal via Ryk/Derailed to repel anterior commissural axons in Drosophila and corticospinal tract axons along the AP body axis in mouse (Yoshikawa et al, 2003;Liu et al, 2005). Conversely, Wnts attract commissural axons after midline crossing in mouse (Lyuksyutova et al, 2003).…”