Geometrical Determinants of Neuronal Actin Waves

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.

Actin Waves Do Not Boost Neurite Outgrowth in the Early Stages of Neuron Maturation

“…Our long-term live cell imaging experiments clearly show that the continuous arrival of AWs generates retraction/growth cycles that, although causing a transient increase of the GC size, do not result in a net neurite elongation (Figures 1 – 3 ). A possible explanation for the discrepancy between our results and what previously reported could be related to the use of P1–P2 hippocampal neurons in our experiments, whereas previous studies used embryonic mouse (E16–E17) or rat (E18) (Flynn et al, 2009 ; Katsuno et al, 2015 ; Winans et al, 2016 ; Tomba et al, 2017 ). Indeed, although neurogenesis continues postnatally, many more neurons are born at the earlier stages and the “older” neurons might exhibit a different behavior.…”

“…(3) What is the mechanism allowing the migration of AWs along the neurites? Indeed, AWs might create tension and exert pulling forces along the neurites (Ruthel and Banker, 1999 ; Lamoureux et al, 2002 ; Tomba et al, 2017 ). In the present manuscript, we use STED nanoscopy and live-cell imaging to tackle these questions.…”

The nano-architecture of the axonal cytoskeleton

“…Besides rings and trails, developing axons also have other intriguing actin assemblies. Actin 'waves' are growthconelike structures that periodically emerge at the base of the axon, travelling along its length, up to the axon tip [149][150][151][152][153][154] (FIG. 2b).…”

The functional architecture of axonal actin

“…Interestingly, more waves travel along the neurite that will become the axon in immature multipolar neurons (Flynn et al, 2009). They could also represent a way to transport actin (Flynn et al, 2009;Tomba et al, 2017), although their low frequency (one or two per hour) and developmental downregulation argue against actin waves as the main vehicle for actin transport (Leterrier et al, 2017).…”