Alteration of neural tissue structure by expression of polysialic acid induced by viral delivery of PST polysialyltransferase.
The expression of polysialic acid (PSA) on neural cell adhesion molecule (NCAM) is known to attenuate cell-cell interactions. During neural development the widespread expression of PSA-NCAM creates permissive conditions for the migration of neuronal and glial precursors and the guidance and targeting of axons. NCAM polysialylation can occur via either of two specific sialyltransferases, ST8SiaII (STX) and ST8SiaIV (PST), and the purpose of this study was to determine if retroviral delivery of either PST or STX could induce PSA expression in vivo and thereby alter tissue plasticity. Retroviruses expressing GFP-PST or GFP-STX were injected into embryonic retina, and development was evaluated by examining neuroepithelial structure, the expression of markers for specific cell types, cellular proliferation, and apoptosis. Chick retina was chosen because it down-regulates PSA early in its development and has a highly stereotyped program of morphogenesis. Retroviral expression of PST induced PSA expression in retina and resulted in severe 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. In contrast, retroviral delivery of STX did not induce PSA expression or affect morphogenesis. These findings demonstrate that expression of PSA is sufficient to promote morphological alterations in a relatively nonplastic neural tissue.
Canger
Anthony K
AK
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Rutishauser
Urs
U
D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D009420:Nervous System / Q000196:embryology; D019006:Neural Cell Adhesion Molecules / Q000235:genetics; D012160:Retina; D012799:Sialyltransferases / Q000235:genetics*
D019006:Neural Cell Adhesion Molecules; C046778:CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase; D012799:Sialyltransferases