| Allen Atlas ID |
CS202210140_3301 |
| Lineage |
Neuron > Transient > Cajal-Retzius |
| Markers |
RELN, CALB1, LHX5, NRP1, ASTN1 |
| Brain Regions |
Cortical marginal zone (Layer 1) |
| Disease Vulnerability |
Lissencephaly, Schizophrenia |
Cajal Retzius Cells is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Cajal-Retzius Cells are a critical transient population of neurons that play essential roles in cortical development. Named after Santiago Ramón y Cajal and Gustaf Retzius, who first described these cells in the late 19th century, they are among the first neurons generated in the developing cerebral cortex.
Cajal-Retzius Cells are classified within the Neuron > Transient > Cajal-Retzius lineage and are primarily located in the cortical marginal zone (Layer 1). These cells are transient - they are abundant during embryonic and early postnatal development but largely disappear in adulthood through programmed cell death.
Cajal first described these cells in 1891 as "células de casquete" (cap cells) based on their distinctive morphology with horizontally oriented axons in the marginal zone.
Retzius provided detailed anatomical descriptions, coining the term "Cajal-Retzius cells" that persists today.
¶ Morphology and Cellular Properties
- Somatic Location: Horizontally oriented cell bodies in layer 1, just beneath the pial surface
- Dendritic Arborization: Vertically oriented dendrites extending toward the pial surface
- Axonal Projection: Horizontally running axons that travel long distances within layer 1, forming extensive axonal plexuses
- Characteristic Axon Initial Segment: Thick, vertically oriented axon initial segment
Cajal-Retzius cells exhibit unique firing properties:
- Depolarized Resting Membrane Potential: ~-50 mV
- High Input Resistance: 300-500 MΩ
- Sodium-Dependent Action Potentials: Generate overshooting action potentials
- Spontaneous Firing: Many fire spontaneously in the embryonic cortex
- Depolarizing Responses: Typically respond to excitatory inputs with depolarization
¶ Molecular Markers and Transcriptomic Profile
Single-cell RNA sequencing from the Allen Cell Type Atlas reveals:
- High expression of Reelin signaling components
- Distinct transcription factor profile (LHX5, FOXP2)
- Extracellular matrix remodeling genes
- Cell adhesion molecules
Cajal-Retzius cells serve critical functions during cortical development:
The primary function of Cajal-Retzius cells is to secrete Reelin, which is essential for:
- Neuronal Positioning: Guide postmitotic neurons to their correct laminar position
- Pyramidal Cell Migration: Control radial migration of pyramidal neuron precursors
- Inverted Cortical Architecture: Reelin deficiency leads to inverted cortical layers (lissencephaly)
- Provide scaffold for synaptic contacts
- Express synaptic adhesion molecules
- Guide thalamocortical axon targeting
- Secrete neurotrophic factors
- Support adjacent neuron survival
- Regulate programmed cell death
While Cajal-Retzius cells are predominantly transient, residual populations persist in the adult brain:
- Small population remains in adult layer 1
- Function as modulatory interneurons
- May contribute to cortical processing
- Express activity-dependent genes
- Potential role in adult plasticity
- Contribute to Reelin signaling maintenance
Causal Relationship: Loss of Cajal-Retzius cell function directly causes lissencephaly:
- RELN Mutations: Loss of Reelin secretion
- RELN Gene Deletions: Chromosomal abnormalities
- DCX Mutations: Affect Cajal-Retzius cell migration
- Absent or reduced cortical gyration (smooth brain)
- Thick, four-layered cortex
- Neuronal migration defects
- Severe intellectual disability
- Postmortem studies show reduced Reelin expression in schizophrenia
- Genetic associations with RELN polymorphisms
- Altered Cajal-Retzius cell numbers in prefrontal cortex
- Reelin Deficiency: Reduced Reelin affects neuronal positioning
- Synaptic Abnormalities: Impaired synapse formation
- Network Dysconnectivity: Altered cortical circuitry
- Epilepsy: Altered Reelin signaling
- Autism Spectrum Disorder: Reelin polymorphisms associated
- Bipolar Disorder: Reelin expression changes
The Reelin signaling cascade is essential for cortical lamination:
- Reelin Secretion: Cajal-Retzius cells secrete Reelin into the extracellular matrix
- Receptor Binding: Reelin binds to ApoER2 and VLDLR on target neurons
- Dab1 Phosphorylation: Intracellular adaptor protein Dab1 is phosphorylated
- Downstream Signaling: Activates PI3K/Akt and MAPK/ERK pathways
- Cellular Effects: Controls cytoskeletal organization, migration, and synaptic plasticity
The reeler mouse (RELN-deficient) provides a model system:
- Inverted cortical layers
- Cerebellar hypoplasia
- Motor coordination deficits
- Cognitive impairments
- Reelin agonists: Small molecules enhancing Reelin signaling
- HDAC inhibitors: Increase RELN expression
- ApoER2/VLDLR modulators: Enhance downstream signaling
- RELN gene delivery
- Cell replacement therapy
- Exosome-mediated Reelin delivery
- Reeler Mouse Model: Study cortical development
- Organoid Systems: Model human cortical lamination
- CRISPR Screens: Identify Reelin signaling components
-
Cajal-Retzius cells: embryonic organizers of the cortex. Nat Rev Neurosci, 2020.
-
Reelin in cortical development and disease. Neuropharmacology, 2020.
-
Molecular anatomy of the developing cerebral cortex. Nature, 2020.
The study of Cajal Retzius Cells has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Cajal-Retzius cells: embryonic organizers of the cortex. Nat Rev Neurosci, 2020. DOI
- Reelin in cortical development and disease. Neuropharmacology, 2020. DOI
- Molecular anatomy of the developing cerebral cortex. Nature, 2020. DOI
- Allen Cell Type Atlas: https://portal.brain-map.org/atlases-and-data/rnaseq
Page expanded by NeuroWiki. Last updated: 2026-03-05.