Reelin and Cajal-Retzius Cells

Cajal-Retzius (CR) cells comprise a population of neurons found in the marginal layer of the developing cerebral cortex and hippocampus of amniotes. Their name originates from their codiscovery in the 1890s by Santiago Ramón y Cajal, who was using Golgi staining techniques on brain sections from small mammals such as rabbits (Ramón y Cajal, 1891), and by Gustaf Retzius, who referred to the cortical marginal cells he observed in human fetuses as “Cajal’s cells” (Retzius, 1893). Despite this common classification, it should be noted that the morphology of CR cells from primates versus small mammals is not homogeneous. Drawings of pri- mate marginal cells provided by Retzius and other authors (Meyer et al., 1999) indicate rather complex and variable morphologies, and Retzius even initially considered “his” CR cells as glia (König, 1978). By contrast, CR cells present in the rat marginal zone—or layer I of the more mature cortex—display fairly homogeneous aspects, so that their identification is straightforward based on three morphologic criteria: fusiform or ovoid shape; bipolarity, i.e., presence of one axon and one dendrite; and tangential orientation of the latter (Fig. 18.1). Due to their facilitated access in a widely used species, a large body of data have been collected regarding the physiologic properties of rat CR cells (Mienville, 1999). In 1995, a novel criterion for identifying these neurons emerged with the discovery of reelin, their secreted protein, which is necessary for correct cortical lamination (D’Arcangelo et al., 1995; Ogawa et al., 1995). While reelin is produced by other cells (see below), certainly the combination of morphologic and immunocytochemical criteria now should allow unambiguous identification of CR cells.