Abstract: |
The expression of polysialic acid (PSA) on neural cell adhesion molecule (NCAM) is known to attenuate cell-cell interactions. During development the widespread expression of PSA-NCAM creates permissive conditions for the migration of neuronal and glial precursors, the guidance and targeting of axons, and synaptogenesis. By contrast, adult expression of PSA is restricted to regions of the nervous system capable of structural plasticity. The purpose of this study was to determine if induced expression of PSA might be sufficient to increase tissue plasticity. We used retroviral expression of ST8SiaIV (PST), an enzyme that catalyzes sialic acid polymerization on NCAM, to produce ectopic PSA in the developing chick retina. This tissue was chosen because it down-regulates PSA early in its highly stereotyped program of morphogenesis. Retinal development was evaluated by examining neuroepithelial structure, expression of markers for specific retinal cell types, cellular proliferation, and apoptosis. PSA misexpression resulted in profound but localized alterations in retinal morphogenesis, including an early disruption of radial glial cell morphology, highly disorganized retinal layers, and invasion of pigmented cells into the neural retina. Cell intrinsic processes such as mitosis and differentiation were not detectably altered, although there was an increase in apoptosis as a consequence of altered morphogenesis. These findings demonstrate that expression of PSA is sufficient to promote morphological alterations in a relatively non-plastic neural tissue. Experiments are now aimed at using the induction of PSA expression by viral delivery of PST to promote plasticity and repair in the adult mouse central nervous system. |