Neuron
Volume 81, Issue 4, 19 February 2014, Pages 814-829
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Article
Pioneering Axons Regulate Neuronal Polarization in the Developing Cerebral Cortex

https://doi.org/10.1016/j.neuron.2013.12.015Get rights and content
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Highlights

  • Neurons are polarized while in contact with the pioneering axons that express TAG-1

  • TAG-1 is required for neuronal polarization

  • Src family kinase Lyn mediates TAG-1-induced neuronal polarization

Summary

The polarization of neurons, which mainly includes the differentiation of axons and dendrites, is regulated by cell-autonomous and non-cell-autonomous factors. In the developing central nervous system, neuronal development occurs in a heterogeneous environment that also comprises extracellular matrices, radial glial cells, and neurons. Although many cell-autonomous factors that affect neuronal polarization have been identified, the microenvironmental cues involved in neuronal polarization remain largely unknown. Here, we show that neuronal polarization occurs in a microenvironment in the lower intermediate zone, where the cell adhesion molecule transient axonal glycoprotein-1 (TAG-1) is expressed in cortical efferent axons. The immature neurites of multipolar cells closely contact TAG-1-positive axons and generate axons. Inhibition of TAG-1-mediated cell-to-cell interaction or its downstream kinase Lyn impairs neuronal polarization. These results show that the TAG-1-mediated cell-to-cell interaction between the unpolarized multipolar cells and the pioneering axons regulates the polarization of multipolar cells partly through Lyn kinase and Rac1.

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