Astrocyte-Associated Fibronectin Is Critical for Axonal Regeneration in Adult White Matter

Abstract

Although it has been suggested that astroglia guide pioneering axons during development, the cellular and molecular substrates that direct axon regeneration in adult white matter have not been elucidated. We show that although adult cortical neurons were only able to elaborate very short, highly branched, dendritic-like processes when seeded onto organotypic slice cultures of postnatal day 35 (P35) rat brain containing the corpus callosum, adult dorsal root ganglion (DRG) neurons were able to regenerate lengthy axons within the reactive glial environment of this degenerating white matter tract. The callosum in both P35 slices and adult rat brain was rich in fibronectin, but not laminin. Furthermore, the fibronectin was intimately associated with the intratract astrocytes. Blockade of fibronectin function in situ with an anti-fibronectin antibody dramatically decreased outgrowth of DRG neurites, suggesting that fibronectin plays an important role in axon regeneration in mature white matter. The critical interaction between regrowing axons and astroglial-associated fibronectin in white matter may be an additional factor to consider when trying to understand regeneration failure and devising strategies to promote regeneration.

Temporally restricted substrate interactions direct fate and specification of neural precursors derived from embryonic stem cells

“…After 14-16 days of maturation, substrate-specific neuronal cell morphologies became apparent. In both conditions, neurons possessed polarized cell bodies with ramified microtubule-associated protein (MAP)-2 ϩ dendritic trees but, consistent with previous reports (19,20), enhanced outgrowth and branching of growth-associated protein (GAP)-43 ϩ axons were observed on LPO substrates (Fig. 2b).…”

Interaction of Thiamine Deficiency and Voluntary Alcohol Consumption Disrupts Rat Corpus Callosum Ultrastructure

“…The greater fiber density may have been the result of fiber deletion, possibly from Wallerian degeneration, or alternatively, regeneration (Tom et al, 2004), likely limited to recovery of small fibers (Wiggins et al, 1985). Our observation of a greater percentage of small fibers in the dually treated rats is consistent with two competing hypotheses: regeneration of small fibers and selective shrinkage or deletion of large fibers.…”

Cells transplanted onto the surface of the glial scar reveal hidden potential for functional neural regeneration

“…In a study where dorsal root ganglion neurons were seeded onto organotypic slices containing the corpus callosum, the donor neurons regenerated lengthy axons along the processes of gliotic astrocytes, and fibronectin expressed on the surface of the astrocytes was an important factor for this regeneration (35). Intriguingly, donor cells appeared able to jump from one astrocytic process to another (35). Such cues are likely to be important for integration of transplanted cells in our model.…”

“…Furthermore, there are numerous intercellular interactions, mediated by molecules such as N-cadherin and neural cell adhesion molecule, which play a crucial role in regenerating and directing axons (34). In a study where dorsal root ganglion neurons were seeded onto organotypic slices containing the corpus callosum, the donor neurons regenerated lengthy axons along the processes of gliotic astrocytes, and fibronectin expressed on the surface of the astrocytes was an important factor for this regeneration (35). Intriguingly, donor cells appeared able to jump from one astrocytic process to another (35).…”