[Corticohistogenesis and Reelin signal cascade]

Corticohistogenesis follows highly regulated spatial and temporal patterns of cell proliferation, neuronal migration and neuronal differentiation to generate the characteristic cortical layers. We gained several insights into the mechanisms of the processes how a class of neurons attains an appropriate layer in developing neocortex. Using a neurological mutant mice reeler, we identified that the extracellular matrix protein Reelin that is specifically secreted from the Cajal-Retzius cells regulates the positioning of the cortical plate neurons. There has identified that Dab1 is one of the intracellular signaling components that respond to Reelin. Recently, three membrane proteins, apoER2, VLDLR and CNR are identified to bind Reelin. The double mutant--apoER2-/-; vldlr-/(-)--shows a phenotype indistinguishable from Reelin deficient mice. The CNRs are originally isolated through the interaction of their intracellular domain with Fyn, a member of the Src kinase family. The antibodies against Reelin or CNR disrupted Reelin-CNR binding. These three classes of membrane proteins are thought to act in concert as components of the Reelin receptor.