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The term Cajal–Retzius cell is applied to reelin-producing neurons of the human embryonic marginal zone which display, as a salient feature, radial ascending processes that contact the pial surface, and a horizontal axon plexus located in the deep marginal zone. These cells were first described by Retzius (Retzius, 1893, 1894). Cajal–Retzius cells possess very long horizontal axons that form asymmetric synaptic contacts with dendritic shafts or spines of neocortical pyramidal cells. Although their exact origin remains a subject of controversy, the caudomedial wall of the telencephalic vesicle has been proposed as the primary source.
Cajal–Retzius cells are found not only in the marginal zone of the human brain but in that of all amniotes, which indicates their evolutionary homology. However, mammalian Cajal–Retzius cells produce substantially higher amounts of reelin, pointing to the spatiotemporal control of reelin expression as a key feature of cortical evolution.
Cajal described in 1891 slender horizontal bipolar cells in the developing marginal zone of lagomorphs.(See the Cajal's original drawing of the cells) These cells were considered by Retzius as homologues to the cells he found in humans and in other mammals (Retzius, 1893, 1894). Similar cells are also present in the rodent marginal zone.
In 2006 a comparison of human and chimpanzees DNA determined that the gene designated HAR1F was the most "Human accelerated region" of the genome. It was determined that the RNA product of the HAR1F gene is expressed in Cajal–Retzius cells.
Role in the cortex
CR cells establish early neuronal circuitry in the developing brain (Aguiló et al., 1999), and express a number of genes known to be important in human cerebral development:
- LIS1 (Clark et al., 1997), which is mutated in lissencephaly;
- EMX2 (Mallamaci et al., 1998);
- RELN (Meyer and Goffinet, 1998). The gene RELN encodes the protein reelin, which is secreted extracellularly by layer I neurones through a constitutive, nonvesicular mechanism (Lacor et al., 2000). This extracellular matrix protein, which is also secreted by Cajal–Retzius neurons, serves as a signal to dissociate for migrating neurons, which travel in clusters, and controls the formation of cortical layers. Lack of reelin, as in the reeler mouse mutant, disturbance of the reelin signaling pathway or ablation of Cajal–Retzius cells causes disorders in cortical lamination.
- P73 protein, a p53-family member involved in the processes of cell survival and apoptosis.
Chameau et al. (2009) report that Cajal–Retzius cells postnatally receive a major excitatory synaptic input via 5-HT3 receptors, and that abolishing this interaction deregulates cortical development, leading to an overgrowth of apical dendrites of layer 2\3 pyramidal cells.
- Retzius G (1893) Die Cajal'schen Zellen der Grosshirnrinde beim Menschen und bei Säugetieren. Biologische Untersuchungen, Neue Folge 5:1–8.
- Retzius G (1894) Weitere Beiträge zur Kenntniss der Cajal'schen Zellen der Grosshirnrinde des Menschen. Biologische Untersuchungen. Neue Folge 6:29–36.
- (1999). What is a Cajal-Retzius cell? A reassessment of a classical cell type based on recent observations in the developing neocortex.. Cerebral cortex (New York, N.Y. : 1991) 9 (8): 765–75.
- ↑ (2004). Generation of reelin-positive marginal zone cells from the caudomedial wall of telencephalic vesicles. Journal of Neuroscience 24 (9): 2286–95.
- ↑ (2000). The evolution of cortical development. An hypothesis based on the role of the Reelin signaling pathway. Trends in neurosciences 23 (12): 633–8.
- ↑ Saito Y, Mizuguchi M, Oka A, Takashima S (2000). Fukutin protein is expressed in neurons of the normal developing human brain but is reduced in Fukuyama-type congenital muscular dystrophy brain. Ann. Neurol. 47 (6): 756–64.
- ↑ (2004). Developmental roles of p73 in Cajal-Retzius cells and cortical patterning.. Journal of Neuroscience 24 (44): 9878–87.
- ↑ Chameau P, Inta D, Vitalis T, Monyer H, Wadman WJ, van Hooft JA (April 2009). The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons. Proc. Natl. Acad. Sci. U.S.A. 106 (17): 7227.
- Feature Article: What is a Cajal–Retzius cell? A Reassessment of a Classical Cell Type Based on Recent Observations in the Developing Neocortex - Cerebral Cortex, Vol. 9, No. 8, 765-775, December 1999
- Active Networks in the Early Brain - "Editors' Choice: Highlights of the recent literature" in the journal Science, 13 September 2002, Vol. 297. no. 5588, p. 1773
- NIF Search - Cajal-Retzius Cell via the Neuroscience Information Framework
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