The earliest cortical neurons have been widely assumed to be the Cajal-Retzius cells, which also spread across the telencephalic surface after tangentially migrating long distances from their birthplaces. Cajal-Retzius cells are most famous for their expression of reelin, which is crucial in guiding the development of the stratified neocortex. The predecessor neurons make no reelin, however, and are thus an entirely new neuron population. Furthermore, the first Cajal-Retzius cells in the emerging human cortex appear a week later than the predecessors. The authors show predecessor and Cajal-Retzius neurons coexisting in the primordial plexiform layer of 7-week-old embryos, with Cajal-Retzius cells coming to lie in the emerging marginal zone above the predecessors.
The new predecessor neurons raise many, many questions. What is their origin, and what is their function? How long do they persist in the developing brain? Could the cortex develop without them? To tackle these issues, analogous early cortical neurons would need to be identified in experimentally amenable species. Unless, of course, the predecessor neurons turn out to be specific to higher primates, which would make them especially interesting. In any case, Bystron and colleagues have opened a new chapter in the developmental biology of the brain, and we eagerly await the sequel.
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