Fig. 8. Effects of PSA on cell interactions and axon fasciculation. (A) When PSA (yellow) is attached to the cell surface via NCAM, its steric properties hinder the apposition of cell membranes and therefore reduce the interaction of receptors, both NCAM (orange) and non-NCAM (blue), on apposing cells. When PSA is removed, receptors can form enough cell-cell bonds for stable adhesion to occur. This steric effect cannot be blocked by soluble PSA. (B) Removal of PSA from the axons and/or their environment can have opposite effects on PSA-positive axon tracts, depending on the nature of the environment. Top: if the environment has powerful and stable adhesive attractants, such as potential sites for junctions (Seki and Rutishauser, 1998), loss of PSA can induce axons to follow more independent, less fasciculated pathways. Bottom: if the environment does not support such stable interactions, as in the matrix-rich plexus region of the chick hindlimb (Tang et al., 1994), the intrinsic interactions among the axons will prevail and loss of PSA will tend to promote growth of axons along other axons to form larger fascicles. In the present study, the PSA-positive posterior commissure, which traverses an environment that contains cells that are also PSA-positive, is shown to defasciculate partially when PSA is removed; this effect is not mimicked by soluble PSA. (C) Two possible binding-based modes for PSA action during midline crossing of commissural axons in the hindbrain. Top: PSA (yellow circles) binds a secreted component (blue circles) necessary for midline crossing, thereby keeping this factor at a high concentration on the surface of floorplate cells. Bottom: a dual binding mechanism in which PSA and a second molecule (blue) on the floorplate cell combine to bind to and activate an axonal receptor. Unlike steric models for PSA action (A,B), the binding-based mechanisms are predicted to be competitively inhibited by soluble PSA and blocked by endo N treatment.
