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Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7227-32. doi: 10.1073/pnas.0810764106. Epub 2009 Apr 6.

The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons.

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  • 1Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, 1090 GE Amsterdam, The Netherlands.


Cajal-Retzius cells, located in layer I of the cortex, synthesize and secrete the glycoprotein reelin, which plays a pivotal role in neuronal migration during embryonic development. Cajal-Retzius cells persist after birth, but their postnatal role is unknown. Here we show that Cajal-Retzius cells receive a major excitatory synaptic input via serotonin 5-HT(3) receptors. Blocking this input using pharmacological tools or neutralization of reelin signaling results in hypercomplexity of apical, but not basal, dendrites of cortical layer II/III pyramidal neurons. A similar hypercomplexity is observed in the cortex of the 5-HT(3A) receptor knockout mouse. The increased dendritic complexity can be rescued by application of recombinant full-length reelin or its N-terminal fragment, but not by the central fragment of reelin, and involves a signal transduction pathway independent of the activation of the canonical reelin receptors. Taken together, our results reveal a novel role of serotonin, Cajal-Retzius cells, and reelin in the postnatal maturation of the cortex.

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