Geometrical Determinants of Neuronal Actin Waves.

Caterina Tomba,Catherine Villard,Benjamin M Friedrich,Nir S Gov,Floriane Cohen,Céline Braïni,Ghislain Bugnicourt

doi:10.3389/fncel.2017.00086

Abstract

Hippocampal neurons produce in their early stages of growth propagative, actin-rich dynamical structures called actin waves. The directional motion of actin waves from the soma to the tip of neuronal extensions has been associated with net forward growth, and ultimately with the specification of neurites into axon and dendrites. Here, geometrical cues are used to control actin wave dynamics by constraining neurons on adhesive stripes of various widths. A key observable, the average time between the production of consecutive actin waves, or mean inter-wave interval (IWI), was identified. It scales with the neurite width, and more precisely with the width of the proximal segment close to the soma. In addition, the IWI is independent of the total number of neurites. These two results suggest a mechanistic model of actin wave production, by which the material conveyed by actin waves is assembled in the soma until it reaches the threshold leading to the initiation and propagation of a new actin wave. Based on these observations, we formulate a predictive theoretical description of actin wave-driven neuronal growth and polarization, which consistently accounts for different sets of experiments.

Highlights

Growing neuronal branches regularly exhibit propagative actin-based membrane deformations, or actin waves, which travel from the cellular body to the neurite tip
Diverse neuronal morphologies were produced from the design of various micropatterns of adhesion, in order to challenge the production of actin waves in situations involving e.g., different neurite widths, or different neurite number
The Neurite Width Controls the Production Rate of Actin Waves Following previous results showing that neurite elongation was slowed down when neurites were allowed to spread on 6 μm, as compared to 2 μm wide stripes (Tomba et al, 2014), we studied the temporal rate of actin wave production in similar geometries of adhesion

Summary

Introduction

Growing neuronal branches (neurites) regularly exhibit propagative actin-based membrane deformations, or actin waves, which travel from the cellular body (soma) to the neurite tip. Actin waves are physiological events generic for a large set of mammalian neurons, e.g., of hippocampal or cortical origin They have been observed both in dissociated neurons in culture and within brain slices (Katsuno et al, 2015; Flynn et al, 2009). Actin waves are associated with outbursts of neurite growth following the possible reactivation of the growth cone, and thereby contribute to the fast elongation of the nascent axon These outbursts result from two successive events occurring at the tip: the tip first retracts as soon as the actin wave leaves the soma, and grows forward when this actin wave merges with the growth cone. It should be noted that fin-like propagative structures similar to neuronal actin waves have been observed in 3T3 cells grown on nanofibers, conferring to these non-neuronal cells neurite-like protrusions (Guetta-Terrier et al, 2015)

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