Endoglycan plays a role in axon guidance by modulating cell adhesion.

Thomas Baeriswyl,Matthias Gesemann,Martina Schaettin,Esther T Stoeckli,Denise Helbling,Georgia Tsapara,Beat Kunz,Evelyn Avilés,Vera Niederkofler,Nicole H Wilson,Alexandre Dumoulin,Jeannine A Frei

doi:10.7554/elife.64767

Abstract

Axon navigation depends on the interactions between guidance molecules along the trajectory and specific receptors on the growth cone. However, our in vitro and in vivo studies on the role of Endoglycan demonstrate that in addition to specific guidance cue - receptor interactions, axon guidance depends on fine-tuning of cell-cell adhesion. Endoglycan, a sialomucin, plays a role in axon guidance in the central nervous system of chicken embryos, but it is neither an axon guidance cue nor a receptor. Rather, Endoglycan acts as a negative regulator of molecular interactions based on evidence from in vitro experiments demonstrating reduced adhesion of growth cones. In the absence of Endoglycan, commissural axons fail to properly navigate the midline of the spinal cord. Taken together, our in vivo and in vitro results support the hypothesis that Endoglycan acts as a negative regulator of cell-cell adhesion in commissural axon guidance.

Highlights

Cell migration and axonal pathfinding are crucial aspects of neural development
Endoglycan was identified as a candidate guidance cue for commissural axons In a subtractive hybridization screen, we identified differentially expressed floor-plate genes as candidate guidance cues directing axons from dorsolateral commissural neurons along the longitudinal axis after midline crossing (Bourikas et al, 2005; see Materials and methods)
Candidates with an expression pattern that was compatible with a role in commissural axon navigation at the midline were selected for functional analysis using in ovo RNAi (Pekarik et al, 2003; Wilson and Stoeckli, 2011). One of these candidates that interfered with the correct rostral turning of commissural axons after midline crossing turned out to be Endoglycan, a member of the CD34 family of sialomucins

Summary

Introduction

Cell migration and axonal pathfinding are crucial aspects of neural development. Neurons are born in proliferative zones from where they migrate to their final destination. At the floor-plate border, commissural axons require the short-range guidance cues Contactin (aka Axonin-1) and NrCAM to enter the midline area (Stoeckli and Landmesser, 1995; Stoeckli et al, 1997; Fitzli et al, 2000; Pekarik et al, 2003). In the same screen that resulted in the discovery of Shh as a repellent for post-crossing commissural axons (Bourikas et al, 2005), we found another candidate that interfered with the rostral turn of postcrossing commissural axons This candidate gene was identified as Endoglycan. Adhesion between growth cones overexpressing Endoglycan and control HEK cells was reduced, in agreement with a model suggesting that Endoglycan acts as a negative regulator of cell-cell adhesion during axon guidance

Results

Discussion

Materials and methods