Mitotic activity in the forebrain subventricular zone is well documented but only in vitro reports suggest the presence of multi-potent stem cells all along the adult mammalian neuraxis. We demonstrate, following cerebroventricular infusion of labeled nucleotides in rat brain, a mitotic activity in the choroid plexus, the ependymal and subependymal layers of the mid- and hindbrain. This proliferation, which probably enables renewal of these structures, was unaffected by the destruction of their serotonergic innervations. Nestin, a marker of immature neural cells, was observed in some proliferative subependymal cells, some classical ependymocytes and in the specialized ependymocytes of the subcommissural organ, the collicular recess and the tanycytes. These observations indicate the presence of immature proliferative cells in the third and fourth periventricular structures, which may generate neural cells.

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SCO-ependymocytes have a secretory activity and a neural innervation relating them to neurosecretory nerve cells. To elucidate the cell lineage of the SCO-ependymocytes and emphasize the role of the neural innervation in their differentiation, in particular 5-HT innervation, we analyzed the developmental pattern of expression of several glial and neuronal markers: (1) in the SCO of mammals possessing (rat, cat) or devoid (mouse, rabbit) of 5-HT innervation, (2) in rat 5-HT deafferented SCO, and (3) in rat SCO transplanted in a foreign environment, the fourth ventricle. The ability of SCO-ependymocytes to transiently express GFAP during development and express the glial alpha alpha-enolase confirms the glial lineage of the SCO-ependymocytes. Synthesis of vimentin by SCO-ependymocytes relates them to the classical ependymocytes. The ability of mature SCO-ependymocytes to take up GABA only when they are innervated by 5-HT terminal underlines the role of the neural environment on the differentiation of these ependymocytes and suggests that differential maturation of the SCO according to its innervation, may lead to specific functional specialization of this organ in different species.