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Neurons of the subpial granular layer (SGL) in the human marginal zone (MZ) migrate tangentially from the periolfactory subventricular zone all over the neocortex. After an immature stage, from 14 to 18 gestational weeks (GW), the SGL attains maximum prominence around midgestation. At 20-25 GW, a transient miniature cell type in the MZ expresses glutamate decarboxylase (GAD) and calretinin, and extends a varicose plexus surrounding somata of large transient Cajal-Retzius neurons (tCRN), potentially modulating their activity. The compact Reelin+ horizontal axon plexus of tCRN forms a transient interface between cortical plate and MZ; it may serve as a migration substrate for cortical interneurons, and attracting NPY+ fibers from the subplate. Around 30 GW, after the disappearance of SGL and tCRN, a population of persisting Cajal-Retzius neurons (pCRN) appears and remains into adult life. pCRNs express Reelin, Tbr1, calretinin, nitric oxide synthase, and the cytokine receptor CXCR4. They are characterized by subpial location, closeness to blood vessels, and aggregation in the walls of developing sulci. Unlike tCRNs, pCRNs do not develop a compact axon plexus in the lower MZ. Occasional mitoses in the midgestation SGL suggest that CRN progenitor cells may give rise to late-appearing pCRNs populating the definitive molecular layer.

The Subpial Granular Layer and Transient Versus Persisting Cajal-Retzius Neurons of the Fetal Human Cortex