Puzzling out the reeler brainteaser: Does reelin signal to unique neural lineages?

Much has been learnt about the reeler mutant since its inclusion in the celebrated Catalog of the Neurological Mutants of the Mouse in the mid-sixties. The pace of discovery was most definitively agitated after the identification of reelin, the genuine gene product mutated in reeler (first expressed by a monolayer of cells in the marginal zone of the developing brain), and the subsequent establishment of the so-called reelin signaling pathway (including the reelin receptor machinery expressed by migrating newborn neurons). Yet little is known as to how the reelin signaling events, which are critically involved in neuronal migration, are linked to the in vivo behavior of individual neurons. Lately, the results of the forced ectopic expression of reelin in the neurogenic zone jeopardized all proposed models regarding its mechanism of action. Our studies suggest that earlier than newborn neurons, the radial glia neuronal progenitors may receive a functional reelin signal. Here I show evidence of an enriched localization of the reelin receptor machinery in radial glial cells of the lateral, but not the median, ganglionic eminence. This precise compartmentalization suggests that, unlike radial migration of cortical projection neurons, reelin signaling is not directly related with the tangential migration of the bulk of cortical interneurons. I hereby submit a personal glimpse of reeler morphogenesis which embodies a testable hypothesis; namely, that reelin signals to unique neural lineages to regulate migration.