Abstract
Reelin, a glycoprotein expressed by Cajal-Retzius neurons throughout the marginal layer of developing neocortex, has been extensively shown to play an important role during brain development, guiding neuronal migration and detachment from radial glia. During the adult life, however, many studies have associated Reelin expression to enhanced neuronal plasticity. Although its mechanism of action in the adult brain remains mostly unknown, Reelin is expressed mainly by a subset of mature interneurons. Here, we confirm the described phenotype of this subpopulation in the adult neocortex. We show that these mature interneurons, although being in close proximity, lack polysialylated neural cell adhesion molecule (PSA-NCAM) expression, a molecule expressed by a subpopulation of mature interneurons, related to brain development and involved in neuronal plasticity of the adult brain as well. However, in the layer II of Piriform cortex there is a high density of cells expressing Reelin whose neurochemical phenotype and connectivity has not been described before. Interestingly, in close proximity to these Reelin expressing cells there is a numerous subpopulation of immature neurons expressing PSA-NCAM and doublecortin (DCX) in this layer of the Piriform cortex. Here, we show that Reelin cells express the neuronal marker Neuronal Nuclei (NeuN), but however the majority of neurons lack markers of mature excitatory or inhibitory neurons. A detail analysis of its morphology indicates these that some of these cells might correspond to semilunar neurons. Interestingly, we found that the majority of these cells express T-box brain 1 (TBR-1) a transcription factor found not only in post-mitotic neurons that differentiate to glutamatergic excitatory neurons but also in Cajal-Retzius cells. We suggest that the function of these Reelin expressing cells might be similar to that of the Cajal-Retzius cells during development, having a role in the maintenance of the immature phenotype of the PSA-NCAM/DCX neurons through its receptors apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR) in the Piriform cortex layer II during adulthood.
Highlights
Reelin is a secreted extracellular matrix glycoprotein, identified 20 years ago by the study of the ‘‘reeler’’ mouse (D’Arcangelo et al, 1995)
We found that the vast majority of Reelin expressing interneurons do not express PSA-NCAM (4.1 ± 2.5%), in very few cases we found a very weak PSA-NCAM expression in Reelin expressing interneurons (Figure 2B)
The detailed analysis of PSA-NCAM expression in the Piriform cortex shows the close proximity of both subpopulations: an upper layer II densely packed with Reelin expressing cells and a lower layer II with a numerous immature neurons expressing PSA-NCAM and DCX (Figure 6A). It reveals the existence of long thick processes forming a pseudo-radial glia that expresses PSA-NCAM (Figure 6A), connecting the lowest part of the external capsule and the layer II of the Piriform cortex, in which end we find the Reelin expressing cells (Figure 6A), resembling the canonical function during development of Reelin expressed by Cajal-Retzius cells
Summary
Reelin is a secreted extracellular matrix glycoprotein, identified 20 years ago by the study of the ‘‘reeler’’ mouse (D’Arcangelo et al, 1995) Previous studies of this particular rodent model found that Reelin is expressed and secreted massively during the early stages of the development by the Cajal-Retzius cells on different brain regions like the neocortex, the hippocampus and the cerebellum (Ogawa et al, 1995; Del Río et al, 1997; Soriano and Del Río, 2005). During this phase, Reelin acts as a chemoattractant of the recently generated neurons, allowing for the correct pattern of neuronal migration and lamination of the main structures of the brain. The Piriform cortex displays a very distinct pattern of expression of Reelin in the rodent adult cortex, the exact phenotype of the Reelin expressing cells in this area remains unknown
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