Extrinsic mechanical forces mediate retrograde axon extension in a developing neuronal circuit

M A Breau,S De Castro,J Stoufflet,I Bonnet,J Xie,S Schneider-Maunoury

doi:10.1038/s41467-017-00283-3

Abstract

To form functional neural circuits, neurons migrate to their final destination and extend axons towards their targets. Whether and how these two processes are coordinated in vivo remains elusive. We use the zebrafish olfactory placode as a system to address the underlying mechanisms. Quantitative live imaging uncovers a choreography of directed cell movements that shapes the placode neuronal cluster: convergence of cells towards the centre of the placodal domain and lateral cell movements away from the brain. Axon formation is concomitant with lateral movements and occurs through an unexpected, retrograde mode of extension, where cell bodies move away from axon tips attached to the brain surface. Convergence movements are active, whereas cell body lateral displacements are of mainly passive nature, likely triggered by compression forces from converging neighbouring cells. These findings unravel a previously unknown mechanism of neuronal circuit formation, whereby extrinsic mechanical forces drive the retrograde extension of axons.

Highlights

To form functional neural circuits, neurons migrate to their final destination and extend axons towards their targets
In the peripheral nervous system, sensory neurons gather from an initial spread distribution of cells to form compact structures: dorsal root ganglia assemble from migrating streams of mesenchymal neural crest cells (NCCs) in the trunk[1], while the progenitors of cranial ganglia and sensory organs coalesce from large regions of the pan-placodal domain
Our findings unravel an unexpected mechanism of neuronal circuit development, where extrinsic mechanical forces drive retrograde axon extension, a wiring strategy that could account for neuronal circuit formation in other regions of the nervous system

Summary

Introduction

To form functional neural circuits, neurons migrate to their final destination and extend axons towards their targets Whether and how these two processes are coordinated in vivo remains elusive. Convergence movements are active, whereas cell body lateral displacements are of mainly passive nature, likely triggered by compression forces from converging neighbouring cells These findings unravel a previously unknown mechanism of neuronal circuit formation, whereby extrinsic mechanical forces drive the retrograde extension of axons. Sensory neurons have to find their position in the neuronal cluster, and to form axons that extend towards and penetrate into the brain or spinal cord at discrete entry points Contacting these intermediate targets is crucial for appropriate innervation of final target regions in the central nervous system. Our findings unravel an unexpected mechanism of neuronal circuit development, where extrinsic mechanical forces drive retrograde axon extension, a wiring strategy that could account for neuronal circuit formation in other regions of the nervous system

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Results

Conclusion