Pioneering axons regulate neuronal polarization in the developing cerebral cortex

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 matri...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2014-02, Vol.81 (4), p.814-829
Main Authors: Namba, Takashi, Kibe, Yuji, Funahashi, Yasuhiro, Nakamuta, Shinichi, Takano, Tetsuya, Ueno, Takuji, Shimada, Akiko, Kozawa, Sachi, Okamoto, Mayumi, Shimoda, Yasushi, Oda, Kanako, Wada, Yoshino, Masuda, Tomoyuki, Sakakibara, Akira, Igarashi, Michihiro, Miyata, Takaki, Faivre-Sarrailh, Catherine, Takeuchi, Kosei, Kaibuchi, Kozo
Format: Article
Language:English
Subjects:
Animals
Axons - metabolism
Cell Adhesion Molecules, Neuronal - metabolism
Cell Differentiation - physiology
Cerebral Cortex - cytology
Cerebral Cortex - growth & development
Cerebral Cortex - metabolism
Contactin 2 - metabolism
Dendrites - metabolism
Grants
Mice
Neurogenesis - physiology
Neurons
Neuropeptides - metabolism
Plasmids
Proteins
rac1 GTP-Binding Protein - metabolism
Science
src-Family Kinases - metabolism
Studies
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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.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2013.12.015