Radial Glial Cell-Neuron Interaction Directs Axon Formation at the Opposite Side of the Neuron from the Contact Site.
How extracellular cues direct axon-dendrite polarization in mouse developing neurons is not fully understood. Here, we report that the radial glial cell (RGC)-cortical neuron interaction directs axon formation at the opposite side of the neuron from the contact site. N-cadherin accumulates at the contact site between the RGC and cortical neuron. Inhibition of the N-cadherin-mediated adhesion decreases this oriented axon formation in vitro, and disrupts the axon-dendrite polarization in vivo. Furthermore, the RGC-neuron interaction induces the polarized distribution of active RhoA at the contacting neurite and active Rac1 at the opposite neurite. Inhibition of Rho-Rho-kinase signaling in a neuron impairs the oriented axon formation in vitro, and prevents axon-dendrite polarization in vivo. Collectively, these results suggest that the N-cadherin-mediated radial glia-neuron interaction determines the contacting neurite as the leading process for radial glia-guided neuronal migration and directs axon formation to the opposite side acting through the Rho family GTPases.
Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Nagoya 466-8550, Japan.
Chundi
C
Xu
Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Nagoya 466-8550, Japan.
Yasuhiro
Y
Funahashi
Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Nagoya 466-8550, Japan.
Takashi
T
Watanabe
Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Nagoya 466-8550, Japan.
Tetsuya
T
Takano
Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Nagoya 466-8550, Japan.
Shinichi
S
Nakamuta
Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Nagoya 466-8550, Japan.
Takashi
T
Namba
Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Nagoya 466-8550, Japan kaibuchi@med.nagoya-u.ac.jp.
Kozo
K
Kaibuchi
D000818:Animals; D001369:Axons / Q000502:physiology*; D015820:Cadherins / Q000378:metabolism; D016764:Cell Polarity; D002540:Cerebral Cortex / Q000166:cytology; D003712:Dendrites; D018274:Electroporation; D063928:Ependymoglial Cells / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008813:Mice, Inbred ICR; D064231:Nestin / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
D015820:Cadherins; D064231:Nestin; D009479:Neuropeptides; C484602:Rac1 protein, mouse; C526380:RhoA protein, mouse; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
N-cadherin; RhoA; axon formation; axon–dendrite polarization; cell–cell interaction; radial glial cell