The surface of the developing cerebral cortex: still special cells one century later

The marginal zone of the developing cerebral cortex is formed by different types of neurons, some of which were described more than one century ago. It is the case of Cajal-Retzius cells, which are known to synthesize and secrete Reelin, an extracellular matrix glycoprotein critically involved in the radial migration and early cortical cytoarchitectonic organization. These cells do not emit projection axons, a characteristic that bespeaks against these cells being considered as pioneer neurons. The true pioneer neurons of the marginal zone are part of a distinct cell entity: these are cells that emit the earliest descending axonal projection from the cerebral cortex into the subpallium, even before than subplate neurons, the other population of pioneer neurons in the cortical anlage. Finally, the marginal zone is a territory where cohorts of undifferentiated cortical interneurons migrate into the upper layers of the cerebral cortex. Marginal zone neurons, including Cajal-Retzius cells, tend to distribute non-uniformly over the cortical surface. Such a mosaic structural configuration points towards more complexities regarding their possible functions during cortical development.