NEURITE OUTGROWTH ON NONPERMISSIVE SUBSTRATES IN-VITRO IS ENHANCED BYECTOPIC EXPRESSION OF THE NEURAL ADHESION MOLECULE L1 BY MOUSE ASTROCYTES

Axonal regrowth in the lesioned central nervous system (CNS) of adult mammals is, in part, prevented by non-permissive properties of glial c ells and myelin. To test if ectopic expression of the neurite outgrowt h promoting recognition molecule L1 will overcome these non-permissive influences and promote neurite outgrowth, L1 was expressed in astrocy tes of transgenic mice using regulatory sequences of the glial fibrill ary acidic protein (GFAP) gene. Northern blot analysis of different tr ansgenic lines revealed different levels of transgenically expressed L 1. Cultured astrocytes derived from transgenic animals displayed L1 im munoreactivity at the cell surface and in situ hybridization and immun ocytochemical analysis of optic nerves from adult transgenic mice loca lized L1 expression to astrocytes. Expression of L1 protein by transge nic astrocytes was significantly upregulated in lesioned optic nerves. When mouse small cerebellar neurons or chick dorsal root ganglion neu rons were cultured on cryosections of lesioned optic nerves or astrocy te monolayers from transgenic mice, respectively, neurite outgrowth wa s increased up to 400% on tissue sections and 50% on astrocytes compar ed with similar preparations from non-transgenic mice. The increase in neurite outgrowth on tissue sections or astrocyte monolayers from dif ferent transgenic lines was proportional to the different levels of L1 expression, Moreover, increased neurite outgrowth on these substrates was specifically inhibited by polyclonal L1 antibodies, In vivo, resc ue of severed axons was enhanced in transgenic versus wild type animal s, while regrowth of axons was slightly, but not significantly, increa sed. Together, our observations demonstrate that L1 promotes neurite o utgrowth when expressed ectopically by astrocytes and that L1 is able to overcome, at least partially, the non-permissive substrate properti es of differentiated CNS glial cells in vitro.