Syk kinases are required for spinal commissural axon repulsion at the midline via the ephrin/Eph pathway

The guidance of axons during embryonic development is likely to involve both adhesive and repulsive interactions between growth cones and their environment. We are characterising the role and mechanism of repulsion during the segmental outgrowth of motor and sensory axons in the somite mesoderm of chick embryos. Axons are confined to the anterior half of each somite by the expression in the posterior half of a glycoconjugate system (48×103Mr and 55×103Mr) that causes the collapse of dorsal root ganglion growth cones when applied in vitro. Enzymatic cleavage of this fraction with specific combinations of endo- and exoglycosidases removes collapse activity, suggesting that carbohydrate residues are involved in the execution of collapse. A similar activity is also detectable in normal adult grey matter, suggesting roles for repulsion beyond the development of spinal nerve segmentation.

Download Full-text

Regulation of axon repulsion by MAX-1 SUMOylation and AP-3

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1804373115 ◽

2018 ◽

Vol 115 (35) ◽

pp. E8236-E8245

Author(s):

Shih-Yu Chen ◽

Chun-Ta Ho ◽

Wei-Wen Liu ◽

Mark Lucanic ◽

Hsiu-Ming Shih ◽

...

Keyword(s):

Axon Guidance ◽

Neural Development ◽

Biochemical Analysis ◽

Genetic Interaction ◽

Motor Axons ◽

Surface Receptors ◽

C Elegans ◽

Guidance Receptors ◽

Axon Repulsion

During neural development, growing axons express specific surface receptors in response to various environmental guidance cues. These axon guidance receptors are regulated through intracellular trafficking and degradation to enable navigating axons to reach their targets. In Caenorhabditis elegans, the UNC-5 receptor is necessary for dorsal migration of developing motor axons. We previously found that MAX-1 is required for UNC-5–mediated axon repulsion, but its mechanism of action remained unclear. Here, we demonstrate that UNC-5–mediated axon repulsion in C. elegans motor axons requires both max-1 SUMOylation and the AP-3 complex β subunit gene, apb-3. Genetic interaction studies show that max-1 is SUMOylated by gei-17/PIAS1 and acts upstream of apb-3. Biochemical analysis suggests that constitutive interaction of MAX-1 and UNC-5 receptor is weakened by MAX-1 SUMOylation and by the presence of APB-3, a competitive interactor with UNC-5. Overexpression of APB-3 reroutes the trafficking of UNC-5 receptor into the lysosome for protein degradation. In vivo fluorescence recovery after photobleaching experiments shows that MAX-1 SUMOylation and APB-3 are required for proper trafficking of UNC-5 receptor in the axon. Our results demonstrate that SUMOylation of MAX-1 plays an important role in regulating AP-3–mediated trafficking and degradation of UNC-5 receptors during axon guidance.

Download Full-text

Complementary expression of transmembrane ephrins and their receptors in the mouse spinal cord: a possible role in constraining the orientation of longitudinally projecting axons

Development ◽

10.1242/dev.127.7.1397 ◽

2000 ◽

Vol 127 (7) ◽

pp. 1397-1410 ◽

Cited By ~ 8

Author(s):

R. Imondi ◽

C. Wideman ◽

Z. Kaprielian

Keyword(s):

Spinal Cord ◽

Floor Plate ◽

Plate Boundaries ◽

Eph Receptors ◽

Axon Pathfinding ◽

Mouse Spinal Cord ◽

Commissural Axon ◽

Ligand Interactions ◽

Ventral Funiculus

In the developing spinal cord, axons project in both the transverse plane, perpendicular to the floor plate, and in the longitudinal plane, parallel to the floor plate. For many axons, the floor plate is a source of long- and short-range guidance cues that govern growth along both dimensions. We show here that B-class transmembrane ephrins and their receptors are reciprocally expressed on floor plate cells and longitudinally projecting axons in the mouse spinal cord. During the period of commissural axon pathfinding, B-class ephrin protein is expressed at the lateral floor plate boundaries, at the interface between the floor plate and the ventral funiculus. In contrast, B-class Eph receptors are expressed on decussated commissural axon segments projecting within the ventral funiculus, and on ipsilaterally projecting axons constituting the lateral funiculus. Soluble forms of all three B-class ephrins bind to, and induce the collapse of, commissural growth cones in vitro. The collapse-inducing activity associated with B-class ephrins is likely to be mediated by EphB1. Taken together, these data support a possible role for repulsive B-class Eph receptor/ligand interactions in constraining the orientation of longitudinal axon projections at the ventral midline.

Download Full-text