Influence of the choroid plexus on cerebellar development: analysis of retinoic acid synthesis

The choroid plexus of the fourth ventricle is conspicuous both in location and size: it protrudes over the outer hindbrain, closely apposed to the caudal external surface of the cerebellum, and it is disproportionately large early on. While the developing cerebellum is known to respond to retinoic acid (RA), it does not express significant levels of RA synthesizing enzyme. Retinaldehyde dehydrogenase levels in the choroid plexus, however, are very high, with maxima during the pre- and postnatal periods of cerebellar morphogenesis. Explants assays demonstrate release of a neurite-outgrowth promoting activity from the choroid plexus, whose levels parallel the levels of RA synthesizing enzyme here, and which can be mimicked by RA. These observations characterize the choroid plexus as a paracrine, growth-promoting organ for the developing cerebellum, with the effects mediated through temporally regulated RA production.