Glutamate-like Immunoreactivity and Fate of Cajal-Retzius Cells in the Murine Cortex as Identified with Calretinin Antibody

Abstract

Cortical layers VI to II develop between two layers of older neurons, the marginal and subplate zones, which are believed to have unique roles in cortical development. While subplate cells have been found essential for the establishment of thalamocortical relationships, the function of the marginal zone and in particular of the neurons of Cajal-Retzius has not been elucidated. Here we show that an antibody against the calcium-binding protein calretinin labels the population of Cajal-Retzius cells throughout their life in the murine cerebral cortex. In prenatal and early postnatal stages, Cajal-Retzius cells were found evenly distributed throughout the murine cerebral cortex. Cajal-Retzius-like neurons were also found in the developing hippocampus and dentate gyrus, which indicates that they may have a general function in cortical development. From P8 onward Cajal-Retzius cells disappeared from the neocortex and hippocampus, at the same time as degenerating immunoreactive neurons were observed. Calretinin-positive Cajal-Retzius cells were glutamate immunoreactive and their presumed axon terminals formed asymmetric synapses. These observations indicate that Cajal-Retzius cells may provide a tonic excitatory input, essential for the maturation of cortical neurons. Furthermore, since neuronal migration has been shown to be dependent on glutamate receptors, we propose that Cajal-Retzius cells releasing glutamate may direct migrating neuroblasts toward the marginal lamina, therefore creating the "inside-out" sequence of cortical development.

Sema3E/PlexinD1 regulates the migration of hem-derived Cajal-Retzius cells in developing cerebral cortex

“…2c). More importantly, after birth, the number of CR cells (eGFP positive) in layer I decreased considerably during the first postnatal week, in line with the natural fate of this cellular population in mice 6 ( Supplementary Fig. 4).…”

“…4b,d). These morphologies with shrunken dendrites and fragmented perikarya have been associated with dying CR cells at these stages 6 .…”

“…These pioneer cells have been largely studied in rodents, feline, primates and human (see refs 3-7). These studies reported that, in mouse neocortex, CR cells largely disappeared during the first postnatal week by programmed cell death 6,8 . During corticogenesis, CR cells seem to play several roles: modulating appropriate migration of cortical plate neurons, actively participating in neuronal network activity in developing marginal zone/layer I, with the capacity to generate action potentials, establishing synaptic contacts in the marginal zone/layer I and receiving excitatory and GABAergic inputs [9][10][11] .…”

Brca1 is required for embryonic development of the mouse cerebral cortex to normal size by preventing apoptosis of early neural progenitors

“…We performed double immunofluorescence for FoxP2, which is predominantly expressed by early-born, deep-layer neurons (Ferland et al, 2003), together with Brn1 (Pou3f3 -Mouse Genome Informatics), which is predominantly expressed by later-born, upper-layer neurons (He et al, 1989;McEvilly et al, 2002), and also for Tbr1, which is strongly expressed by layer VI and layer III neurons (Bulfone et al, 1995;Hevner et al, 2001), together with Brn2 (Pou3f2), which is predominantly expressed by later-born, upper-layer neurons (He et al, 1989;McEvilly et al, 2002). This revealed the preservation of cortical layering in the conditional Brca1 knockout, with Brn1 + and Brn2 + neurons still preferentially found in the upper layers and FoxP2 + and Tbr1 + neurons preferentially in the deeper layers ( Fig Cortical organization was further examined by immunofluorescence staining on P4.5 coronal brain sections for calretinin (calbindin 2), which, at early postnatal stages, is expressed 1861 RESEARCH ARTICLE Brca1 and neocortical development DEVELOPMENT 1862 by neurons in layer I (specifically Cajal-Retzius cells) (Del Río et al, 1995;Fonseca et al, 1995), pyramidal-like neurons in layer V (Schierle et al, 1997) and interneurons (Rogers, 1992;Wonders and Anderson, 2006). The abundance and organization of calretinin + neurons appeared unaffected in the Brca1-ablated neocortex as compared with the control (see Fig.…”

“…Cortical organization was further examined by immunofluorescence staining on P4.5 coronal brain sections for calretinin (calbindin 2), which, at early postnatal stages, is expressed by neurons in layer I (specifically Cajal-Retzius cells) (Del Río et al, 1995;Fonseca et al, 1995), pyramidal-like neurons in layer V (Schierle et al, 1997) and interneurons (Rogers, 1992;Wonders and Anderson, 2006). The abundance and organization of calretinin + neurons appeared unaffected in the Brca1-ablated neocortex as compared with the control (see Fig.…”