Radial Glial Cell–Neuron Interaction Directs Axon Formation at the Opposite Side of the Neuron from the Contact Site

摘要

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.>SIGNIFICANCE STATEMENT Neurons are highly polarized cell lines typically with a single axon and multiple dendrites, which underlies the ability of integrating and transmitting the information in the brain. How is the axon–dendrite polarity of neurons established in the developing neocortex? Here we show that the N-cadherin-mediated radial glial cell–neuron interaction directs axon–dendrite polarization, the radial glial cell–neuron interaction induces polarized distribution of active RhoA and active Rac1 in neurons, and Rho–Rho-kinase signaling is required for axon–dendrite polarization. Our work advances the overall understanding of how extracellular cues direct axon–dendrite polarization in mouse developing neurons.