Direct interaction with target-derived glia enhances survival but not differentiation of human fetal mesencephalic...

Regulation of the developing nervous system involves attraction, guidance and modification of innervating neurons by target cells through diffusible and membrane-related factors. The trophic effects from specific cell types remain to be investigated and characterized. In a series of experiments in which human fetal mesencephalic dopaminergic cells were co-cultured with target or non-target neurons or glial cells in direct or contiguous contact, we demonstrate that striatal glial cells (target-derived glia) can enhance dopaminergic neuron survival by up to 400% compared to either non-target cell co-cultures or mesencephalic controls. When in direct contact with striatal neurons, a greater proportion of dopaminergic neurons had a more differentiated morphology. The enhancement of dopaminergic neuron survival by target-derived glia appears to be mediated both by direct contact, possibly through target membrane-specific phenomena, and by diffusible substances, whereas non-target glia appear to exert the trophic effects predominantly through the latter mechanism. The finding that target neurons influence mainly dopaminergic neuron differentiation and target glia their survival indicates multiple, target cell type-specific regulation of innervating neuron development. These findings also have relevance to the establishment of neuronal cultures for neural transplantation.