Regional and Cellular Patterns ofreelinmRNA Expression in the Forebrain of the Developing and Adult Mouse

Abstract

The reelin gene encodes an extracellular protein that is crucial for neuronal migration in laminated brain regions. To gain insights into the functions of Reelin, we performed high-resolution in situ hybridization analyses to determine the pattern of reelin expression in the developing forebrain of the mouse. We also performed double-labeling studies with several markers, including calcium-binding proteins, GAD65/67, and neuropeptides, to characterize the neuronal subsets that express reelin transcripts. reelin expression was detected at embryonic day 10 and later in the forebrain, with a distribution that is consistent with the prosomeric model of forebrain regionalization. In the diencephalon, expression was restricted to transverse and longitudinal domains that delineated boundaries between neuromeres. During embryogenesis, reelin was detected in the cerebral cortex in Cajal-Retzius cells but not in the GABAergic neurons of layer I. At prenatal stages, reelin was also expressed in the olfactory bulb, and striatum and in restricted nuclei in the ventral telencephalon, hypothalamus, thalamus, and pretectum. At postnatal stages, reelin transcripts gradually disappeared from Cajal-Retzius cells, at the same time as they appeared in subsets of GABAergic neurons distributed throughout neocortical and hippocampal layers. In other telencephalic and diencephalic regions, reelin expression decreased steadily during the postnatal period. In the adult, there was prominent expression in the olfactory bulb and cerebral cortex, where it was restricted to subsets of GABAergic interneurons that co-expressed calbindin, calretinin, neuropeptide Y, and somatostatin. This complex pattern of cellular and regional expression is consistent with Reelin having multiple roles in brain development and adult brain function.

Age-related accumulation of Reelin in amyloid-like deposits

“…1, 4) is in accordance with previous studies, revealing its expression in GABAergic interneurons, adult Cajal-Retzius cells, and pyramidal cells in layer II of the entorhinal cortex in rodents and humans (Abraham and Meyer, 2003;Alcantara et al, 1998;Miettinen et al, 2005;Ramos-Moreno et al, 2006;Riedel et al, 2003). The prominent loss of Reelin neurons in CA so, slm and DG ml is in line with reductions in the GABAergic markers GAD 67 , Calbindin, and Somatostatin in the aged rat hippocampus (Potier et al, 1994;Shetty and Turner, 1998), and Somatostatin/NPY in APP/PS1 transgenic mice .…”

“…The signal is terminated with Reelin targeted to the lysosome and Dab1 degraded by the proteasome (Arnaud et al, 2003;Bock et al, 2004;Morimura et al, 2005). In the adult brain, Reelin expression is maintained by GABAergic interneurons and glutamatergic pyramidal neurons in layer II of the entorhinal cortex (Alcantara et al, 1998;Miettinen et al, 2005;Pesold et al, 1998;Ramos-Moreno et al, 2006) and the same signalling cascade is used in adult synapses to modulate neuronal function and synaptic plasticity by regulating glutamate receptor activity through the phosphorylation of intracellular tyrosine residues (Beffert et al, , 2006Chen et al, 2005;Weeber et al, 2002).…”

Mouse orthologue of ARX, a gene mutated in several X‐linked forms of mental retardation and epilepsy, is a marker of adult neural stem cells and forebrain GABAergic neurons

“…In adult brain, Arx-positive cells were found scattered throughout the mature cerebral cortex, similarly to the cells expressing reelin and GAD1, well-known molecular markers of adult GABAergic neurons (Alcantara et al, 1998). Thus, supposing that Arx-positive neurons in the cortex were probably GABAergic neurons, we performed colabeling stainings with Arx and markers of mature and functional interneurons.…”

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

“…1C), where it modulates spine dynamics and synaptic plasticity, as well as suppresses Tau hyperphosphorylation (Herz and Chen, 2006, Forster et al, 2010, Knuesel, 2010. As documented previously (Alcantara et al, 1998, Martinez-Cerdeno et al, 2002, Ramos-Moreno et al, 2006, Reelin is expressed by granule, mitral and tufted cells of the olfactory bulb. Its immunoreactivity can be further detected along the long projections of the latter two principal cell types: the lateral olfactory tract and olfactory tubercle, as well as in the neuropil of their projection areas: anterior olfactory nucleus, amygdala, piriform and entorhinal cortex.…”

“…Further, Reelin is produced by the pyramidal cells of the piriform and entorhinal cortex projecting to thalamus and hippocampus, respectively. In the hippocampus itself, Reelin expression is restricted to local interneurons (Alcantara et al, 1998, Koliatsos et al, 2004, Ramos-Moreno et al, 2006, Knuesel et al, 2009. Finally, Reelin is also expressed in the corticomedial amygdaloid nuclei and the paraventricular nuclei of the thalamus.…”