Retinoids are produced by glia in the lateral ganglionic eminence and regulate striatal neuron differentiation

In order to identify molecular mechanisms involved in striatal development, we employed a subtraction cloning strategy to enrich for genes expressed i n the lateral versus the medial ganglionic eminence. Using this approach, t he homeobox gene Meis2 was found highly expressed in the lateral ganglionic eminence and developing striatum, Since Meis2 has recently been shown to b e upregulated by retinoic acid in P19 EC cells (Oulad-Abdelghani, M., Chaza ud, C., Bouillet, P., Sapin, V,, Chambon, P, and Dolle, P. (1997) Dev. Dyn. 210, 173-183), we examined a potential role for retinoids in striatal deve lopment, Our results demonstrate that the lateral ganglionic eminence, unli ke its medial counterpart or the adjacent cerebral cortex, is a localized s ource of retinoids, Interestingly, glia (likely radial glia) in the lateral ganglionic eminence appear to be a major source of retinoids, Thus, as lat eral ganglionic eminence cells migrate along radial glial fibers into the d eveloping striatum, retinoids from these glial cells could exert an effect on striatal neuron differentiation. Indeed, the treatment of lateral gangli onic eminence cells with retinoic acid or agonists for the retinoic acid re ceptors or retinoid X receptors, specifically enhances their striatal neuro n characteristics. These findings, therefore, strongly support the notion t hat local retinoid signalling within the lateral ganglionic eminence regula tes striatal neuron differentiation.