Figure 7.

Schematic model for temporal interactions between reactive astrocytes and meningeal fibroblasts along the surface of the lesioned spinal cord. A, Three days after lesion, meningeal fibroblasts migrating into the lesion cavity begin making contact with astrocytes (yellow glow) along the lesioned surface of the spinal cord. In response to direct cell contact (inset), ephrin-B2 ligands on the surface of astrocytes bind to EphB2 receptors on invading fibroblasts, resulting in the phosphorylation of the tyrosine kinase domain on EphB2 (red receptors) and phosphorylation of conserved tyrosine residues on the cytoplasmic domain of ephrin-B2 (blue triangles). Receptor-ligand phosphorylation results in the initiation of bidirectional intracellular signaling cascades within the meningeal fibroblasts and reactive astrocytes. We propose that stimulation of EphB2 on the meningeal fibroblasts activates the Rho-GTPase pathway, producing local actin depolymerization that prevents additional infiltration of the fibroblasts into the spinal cord parenchyma. Activation of additional bidirectional signaling cascades in astrocytes and fibroblasts may initiate gene transcription for the deposition of ECM components by both cell types along their interface. B, Seven days after lesion, ECM components secreted by reactive astrocytes and meningeal fibroblasts form a basal lamina along areas of previous glial-meningeal contact. The deposition of this ECM prevents additional contact between ephrin-B2 and EphB2, resulting in a decrease in the endogenous phosphorylation and activation of EphB2 receptors on meningeal fibroblasts and ephrin-B2 on astrocytes. This decreased activation of the Ephephrin pathways may result in enhanced signaling through integrin receptor binding to the ECM components in the basal lamina, stabilizing the glial-meningeal boundary. C, Fourteen days after lesion. By this time, a basal lamina has completely formed along the glial-meningeal interface, and signaling between ephrin-B2 and EphB2 is terminated. Integrin-mediated binding of astrocytes and meningeal fibroblasts to the basal lamina now maintains the integrity of the glial-meningeal boundary.