Differences in Cajal-Retzius cell density and postnatal persistence across cortical areas revealed by a novel intersectional genetic labeling approach

Cajal-Retzius (CR) cells are glutamatergic neurons that transiently populate the most superficial layer of the isocortex and allocortex during development, serving an essential role during both prenatal and early postnatal brain development. Notably, these cells disappear from most cortical areas by postnatal day 14, but persist for much longer in the hippocampus. We developed a novel intersectional genetic labeling approach for CR cells that captures almost all of the TRP73-positive CR cells throughout the isocortex and allocortex. This intersectional strategy offers several advantages over previous methods commonly used for CR cell targeting. Here, we applied this new CR cell labeling strategy to investigate the distribution and persistence of CR cells throughout the whole mouse brain, at four different postnatal ages. We observed that the initial CR cell density and the rate of their disappearance varies substantially across different brain areas during development. Strikingly, we observed variation in cell death rate even between adjacent cortical subregions: comparing the medial and the lateral entorhinal cortex, the former retains a high density of CR cells for several months in contrast to the latter. Our results present a necessary revision of the phenomenon of CR cell persistence, showing that, in addition to hippocampus, several other cortical areas maintain a high density of these cells beyond the first two postnatal weeks.