Role of Thy‐1 in in vivo and in vitro neural development and regeneration of dorsal root ganglionic neurons

Abstract

We have examined the expression of Thy-1, an abundant glycosylphosphatidylinositol (GPI)-anchored glycoprotein, in dorsal root ganglia (DRG) and associated nerve fascicles, during postnatal development and following a nerve crush. The expression levels of Thy-1 in DRG neurons, dorsal roots, and central processes in spinal cord were rather low at postnatal day 2, and gradually increased as DRG neurons matured. During early development, the expression of Thy-1 within DRG neurons was low and equally distributed between plasma membrane and cytosol. With maturation, the staining intensities of Thy-1 in both the plasma membrane and the cytosol of DRG neurons became increased. We also studied Thy-1 expression in the regeneration of mature DRG neurons following the crush injury of sciatic nerve. Two days after the crush injury, Thy-1 expression dramatically decreased in the DRG neurons on the lesion side. Between 4 and 7 days after the injury, the expression of Thy-1 gradually increased and returned to a normal level 1 week after the sciatic nerve crush. The time course of the up-regulation of Thy-1 expression during regeneration matched that of the recovery of sensory functions, such as pain withdraw reflex, placing reflex, and the score of Basso-Beattie-Bresnahan Locomotor Rating Scale. Taken together, our results suggest that Thy-1 expression is developmentally regulated and is closely associated with the functional maturation of DRG neurons during both postnatal development and nerve regeneration. Furthermore, perturbation of Thy-1 function with anti-Thy-1 antibodies promoted neurite outgrowth from primary cultured DRG neurons, again confirming the inhibitory role of Thy-1 on neurite outgrowth.

Perinatal asphyxia: current status and approaches towards neuroprotective strategies, with focus on sentinel proteins

“…Thy-1 has been considered to be a cell adhesion molecule belonging to the immunoglobulin superfamily. However, many studies now support the idea that Thy-1 plays the role of an inhibitory protein modulating axonal growth (Morris et al 1992; Chen et al 2005). Indeed, it has been suggested that Thy-1 limits axonal growth in order to stabilize neuronal connections during postnatal development (Morris et al 1992; Barlow and Huntley 2000).…”

Astrocytic αVβ3 Integrin Inhibits Neurite Outgrowth and Promotes Retraction of Neuronal Processes by Clustering Thy-1

“…For instance, cells of neural origin, like PC12 and NG115, increase the extension of neuronal-like processes when lacking Thy-1 [4], [5]. Recently, Thy-1-mediated inhibition of neurite outgrowth was suggested to impair neuronal regeneration in vivo [6]–[8]. Indeed, a decrease in Thy-1 levels might be required in regeneration of dorsal root ganglion neurons following injury of the sciatic nerve in adult rats [6].…”

“…Recently, Thy-1-mediated inhibition of neurite outgrowth was suggested to impair neuronal regeneration in vivo [6]–[8]. Indeed, a decrease in Thy-1 levels might be required in regeneration of dorsal root ganglion neurons following injury of the sciatic nerve in adult rats [6]. Part of the “scientific facelessness” of Thy-1 stems from the lack of a defined ligand [1].…”

Anti‐Thy‐1 antibody‐induced neurite outgrowth in cultured dorsal root ganglionic neurons is mediated by the c‐Src‐MEK signaling pathway

“…Ascites containing mouse monoclonal antiThy-1 antibody [Jeng et al, 1998] at a fina1 dilution of 1:20 in culture medium was applied for the indicated time to day 2 cultures as described by Chen et al [2005]. Either normal mouse serum or an irrelevant mouse monoclonal antibody was used as controls.…”