Abstract

Establishment and maintenance of neuronal polarity are critical for neuronal development and function. One of the fundamental questions in neurodevelopment is how neurons generate only one axon and several dendrites from multiple minor neurites. Over the past few decades, molecular and cell biological approaches have unveiled a large number of signaling networks regulating neuronal polarity in cultured hippocampal neurons and the developing cortex. Emerging evidence reveals that positive and negative feedback signals play a crucial role in axon and dendrite specification. Positive feedback signals are continuously activated in one of minor neurites and result in axon specification and elongation, whereas negative feedback signals are propagated from a nascent axon terminal to all minor neurites and inhibit the formation of multiple axon, thereby leading to dendrite specification, and maintaining neuronal polarity. This current insight provides a holistic picture of the signaling mechanisms underlying neuronal polarization during neuronal development. Here, our review highlights recent advancements in this fascinating field, with a focus on the positive, and negative feedback signals as key regulatory mechanisms underlying neuronal polarization.

Highlights

  • Cell polarization is a crucial step in multiple cellular aspects such as differentiation, morphogenesis, and migration

  • Negative feedback signals that are delivered from the nascent axon induce dendritic specification in cultured hippocampal neurons, some neurons that do not have axons by knockout of transforming growth factor-β (TGF-β) receptor or LKB1 show dendrite formation in the developing cortex (Barnes et al, 2007; Yi et al, 2010)

  • These findings suggest that additional molecular mechanisms might be involved in dendritic specification in vivo

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Summary

Introduction

Cell polarization is a crucial step in multiple cellular aspects such as differentiation, morphogenesis, and migration. The TAG1-mediated neuron-neuron interaction activates Rac1 at the minor neurite of the MP cell through the Src family kinase Lyn and induces axon initiation (Namba et al, 2014; Figure 2A). The PI3-kinase/Cdc42/Par complex/RacGEF/Rac1 pathway represents a positive-feedback loop that responsible for axon specification (Arimura and Kaibuchi, 2007; Takano et al, 2015; Figure 2B).

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