Calcium Signaling during Cortical Apical Dendrite Initiation: A Role for Cajal-Retzius Neurons

Area of Science:

• Neuroscience
• Developmental Biology
• Cellular Signaling

Background:

• Cortical projection neurons (CPNs) develop their apical dendrites from their leading process upon completing migration in the marginal zone (MZ).
• Cajal-Retzius neurons (CRNs) in the MZ secrete Reelin, crucial for dendrite development and cell positioning.
• The MZ may harbor additional CRN-derived signals that promote CPN maturation and cortical development.

Purpose of the Study:

• To investigate potential CRN-secreted signals that influence CPN maturation and cortical development.
• To elucidate the communication pathways between CRNs and CPNs during early corticogenesis.

Main Methods:

• Utilized whole embryonic hemisphere explants and multiphoton microscopy to observe intracellular calcium transients in CRNs and CPNs.
• Applied veratridine, a sodium channel activator, to stimulate CRNs and assess its effect on CPNs.
• Employed receptor antagonists (glutamate, glycine) and genetic manipulation (bacterial voltage-gated calcium channel) to study signaling mechanisms.

Main Results:

• CRNs exhibit spontaneous, high-amplitude intracellular calcium transients during early corticogenesis.
• CPNs show a steady increase in intracellular calcium upon dendritic initiation, triggered by CRN activity via glutamate and glycine.
• Glutamatergic signaling blockade disrupts CPN migration; forced calcium channel expression promotes dendritic growth but arrests migration.

Conclusions:

• CRN spontaneous activity triggers glutamate and glycine release, inducing calcium elevations in CPNs that initiate dendritogenesis and propagate.
• CRN-to-CPN signaling plays a role in CPN migration and dendritic development.
• This signaling pathway provides a potential link to autism-linked genes encoding synaptic proteins expressed early in cortical development.