Cajal-Retzius and subplate neurons: their role in cortical development

Cajal-Retzius (C-R) neurons and their processes form a synaptic network in the marginal zone of the early telencephalon prior to the arrival of the first wave of radial migration of neuroblasts from the subventricular zone. Their origin is not yet proved but may be either the medial ganglionic eminence or the mesencephalic neuromere. These bipolar or multipolar neurons populate the molecular layers of both the fetus and the adult, though sparse in the adult. Their thick axon emits collaterals that make synaptic contact with pyramidal neurons initially in layer 6 and later within all layers. C-R neurons produce GABA, possibly ACh, several calcium-binding proteins (e.g. calmodulin; parvalbumin; possibly calretinin), several neuropeptides and are rich in ribosomes. Subplate neurons, beneath the cortical plate, emit pioneer axons in the incipient formation of the internal capsule and also commissural fibres of the early hippocampus. C-R cells express products of the genes reelin, LIS1 and DS-CAM, that mediate radial neuroblast migration and lamination of the cortical plate and are important in the pathogenesis of lissencephaly. In addition to forming the first intrinsic synaptic circuits of the cortical plate and its first afferent and efferent connections with subcortical structures, they may play additional roles in the formation of ocular dominance columns, in regulating neuronogenesis and in cortical repair. They do not later disappear by apoptosis as we previously thought, but their functional role in the mature brain is unknown.