EXPRESSION OF L1 IN PRIMARY ASTROCYTES VIA A DEFECTIVE HERPES-SIMPLEXVIRUS VECTOR PROMOTES NEURITE OUTGROWTH AND NEURAL CELL-MIGRATION

The neural cell adhesion molecule L1 is a transmembrane glycoprotein o f approximately 200 kDa molecular weight that is a member of the immun oglobulin super family. Multiple functions of L1 have been reported, i ncluding cell-cell interactions, neurite elongation, axonal fasciculat ion, cell migration, and myelination. L1 plays important roles in neur al development and axonal regeneration in the peripheral nervous syste m (PNS), however in the adult it is only present on neurons in the cen tral nervous system (CNS). In the present study we have used defective herpes simplex virus (HSV) vectors to express full-length human or ra t LI in cultured primary rat cortical astrocytes. Rat cerebellar granu le cells, a rather homogeneous population of neurons, co-cultured on a substrate layer of L1-expressing astrocytes demonstrated increased mi gration and neurite extension compared with neurons co-cultured on lac Z-expressing astrocytes or uninfected astrocytes. There was no detecta ble difference between human and rat L1. Because this vector system ca n be used to confer phenotypic changes in primary nervous system cells it will be useful for in vitro and in vivo studies of neural regenera tive sprouting and plasticity in the CNS.