Expression of L1 in primary astrocytes via a defective herpes simplex virus vector promotes neurite outgrowth and neural cell migration

The neural cell adhesion molecule L1 is a transmembrane glycoprotein of approximately 200 kDa molecular weight that is a member of the immunoglobulin super family. Multiple functions of L1 have been reported, including cell-cell interactions, neurite elongation, axonal fasciculation, cell migration, and myelination. L1 plays important roles in neural development and axonal regeneration in the peripheral nervous system (PNS), however in the adult it is only present on neurons in the central nervous system (CNS). In the present study we have used defective herpes simplex virus (HSV) vectors to express full-length human or rat LI in cultured primary rat cortical astrocytes. Rat cerebellar granule cells, a rather homogeneous population of neurons, co-cultured on a substrate layer of L1-expressing astrocytes demonstrated increased migration and neurite extension compared with neurons co-cultured on lacZ-expressing astrocytes or uninfected astrocytes. There was no detectable difference between human and rat L1. Because this vector system can be used to confer phenotypic changes in primary nervous system cells it will be useful for in vitro and in vivo studies of neural regenerative sprouting and plasticity in the CNS.