The Eph family of tyrosine kinase receptors and ligands play key roles in c
ell segregation and axon targeting in the developing nervous system. Intera
ctions between the ligands and receptors cause repulsion or degeneration of
receptor-positive axons from several brain regions including the retina, h
ippocampus, thalamus, and midbrain dopaminergic system. We extend these pre
vious observations by showing that three A-ephrins also negatively regulate
the growth of neurites from striatal and olfactory neurons. In addition to
negative effects, however, we also report a trophic activity of the A-ephr
ins: Ephrin-A2 and A5 promote survival and neurite outgrowth of sympathetic
neurons. These observations provide support to the notion that ephrins may
function as either negative or positive signals in the developing nervous
system. (C) 2000 Wiley-Liss, Inc.