Tissue-specific neuro-glia interactions determine neurite differentiation in ganglion cells

Guided formation and extension of axons versus dendrites is considered cruc ial for structuring the nervous system. In the chick visual system, retinal ganglion cells (RGCs) extend their axons into the tectum opticum, but not into glial somata containing retina layers. We addressed the question wheth er the different glia of retina and tectum opticum differentially affect ax on growth. Glial cells were purified from retina and tectum opticum by comp lement-mediated cytolysis of non-glial cells. RGCs were purified by enzymat ic delayering from Rat mounted retina. RGCs were seeded onto retinal versus tectal glia monolayers. Subsequent neuritic differentiation was analysed b y immunofluorescence microscopy and scanning electron microscopy. Qualitati ve and quantitative evaluation revealed that retinal glia somata inhibited axons. Time-lapse video recording indicated that axonal inhibition was base d on the collapse of lamellipodia- and filopodia-rich growth cones of axons . In contrast to retinal glia, tectal glia supported axonal extension. Nota bly, retinal glia were not inhibitory for neurons in general, because in co ntrol experiments axon extension of dorsal root ganglia was not hampered, T herefore, the axon inhibition by retinal glia was neuron type-specific. In summary, the data demonstrate that homotopic (retinal) glia somata inhibit axonal outgrowth of RGCs, whereas heterotopic (tectal) glia of the synaptic target area support RGC axon extension. The data underscore the pivotal ro le of glia in structuring the developing nervous system.