Local Translation Across Neural Development: A Focus on Radial Glial Cells, Axons, and Synaptogenesis.

Manasi Agrawal,Kristy Welshhans

doi:10.3389/fnmol.2021.717170

Manasi Agrawal, Kristy Welshhans

Open Access

https://doi.org/10.3389/fnmol.2021.717170

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Abstract

In the past two decades, significant progress has been made in our understanding of mRNA localization and translation at distal sites in axons and dendrites. The existing literature shows that local translation is regulated in a temporally and spatially restricted manner and is critical throughout embryonic and post-embryonic life. Here, recent key findings about mRNA localization and local translation across the various stages of neural development, including neurogenesis, axon development, and synaptogenesis, are reviewed. In the early stages of development, mRNAs are localized and locally translated in the endfeet of radial glial cells, but much is still unexplored about their functional significance. Recent in vitro and in vivo studies have provided new information about the specific mechanisms regulating local translation during axon development, including growth cone guidance and axon branching. Later in development, localization and translation of mRNAs help mediate the major structural and functional changes that occur in the axon during synaptogenesis. Clinically, changes in local translation across all stages of neural development have important implications for understanding the etiology of several neurological disorders. Herein, local translation and mechanisms regulating this process across developmental stages are compared and discussed in the context of function and dysfunction.

Highlights

Neurons are highly polarized cells with extensive spatial compartmentalization
During the stages of guidance and synaptogenesis, we focus on axons and the formation of presynaptic terminals; local translation in dendrites is beyond the scope of this review
Of this review, we focus on additional studies examining four functional categories that these large scale studies have shown are enriched in developing axons and growth cones: cell adhesion molecules, transcription factors, protein synthesis machinery, and cytoskeletal-related proteins (Figure 2)

Summary

Introduction

Neurons are highly polarized cells with extensive spatial compartmentalization. The long and complex nature of these cells requires that distal axons and dendrites respond to external cues rapidly, without direct communication with the soma. Recent in vitro and in vivo studies have provided new information about the specific mechanisms regulating local translation during axon development, including growth cone guidance and axon branching. A key mechanism regulating this dynamic signaling is the localization of translational machinery, including mRNA transcripts, ribosomes, and RNA-binding proteins (RBPs), to subcellular regions of developing neurons (Jung et al, 2014; Holt et al, 2019).

Results

Conclusion