Induction of astrocyte differentiation by endothelial cells

Here we have investigated the mechanisms that control astrocyte differentia tion within the developing rat optic nerve. Astrocytes are normally generat ed by astrocyte precursor cells within the embryonic optic nerve. We show t hat there is a close temporal and spatial correlation between endothelial a nd astrocyte differentiation. We tested the potential role of endothelial c ells in inducing astrocyte differentiation by developing an immunopanning m ethod to highly purify endothelial cells from developing optic nerves. We s how that the purified endothelial cells, but not other embryonic optic nerv e cell types, strongly induce the differentiation of purified astrocyte pre cursor cells into astrocytes in vitro. Leukemia inhibitory factor (LIF) and LIF receptors have been implicated previously in astrocyte differentiation in vivo. We show that purified endothelial cells express LIF mRNA and that their ability to induce astrocyte differentiation is prevented by a neutra lizing anti-LIF, but not anti-ciliary neurotrophic factor, antiserum. These findings demonstrate a role for endothelial cells in inducing astrocyte di fferentiation. The induction of astrocyte differentiation by endothelial ce lls makes sense phylogenetically, anatomically, and functionally, because a strocytes evolved concurrently with brain vasculature and ensheathe capilla ries throughout the brain. The ability to purify and culture astrocytes and endothelial cells should provide an excellent model system for future stud ies of blood-brain barrier development.