Pierre Recho

Cortical instability drives periodic supracellular actin pattern formation in epithelial tubes

Significance Robust pattern formation is a ubiquitous question of developmental biology. In 1952, Turing proposed in a seminal paper that this could be achieved by a hydrodynamical instability of two diffusing species reacting with each other, but direct experimental evidence of how a mechanism is implemented biologically is still lacking. In this paper, we show by a combination of experiment and theory that the actin cytoskeleton, one of the main force-producing mechanisms in biology, has the property to self-organize into regular supracellular patterns in vivo in Drosophila. We show that the wavelength of the pattern depends on the physical properties of the gel and can be modified experimentally. An essential question of morphogenesis is how patterns arise without preexisting positional information, as inspired by Turing. In the past few years, cytoskeletal flows in the cell cortex have been identified as a key mechanism of molecular patterning at the subcellular level. Theoretical and in vitro studies have suggested that biological polymers such as actomyosin gels have the property to self-organize, but the applicability of this concept in an in vivo setting remains unclear. Here, we report that the regular spacing pattern of supracellular actin rings in the Drosophila tracheal tubule is governed by a self-organizing principle. We propose a simple biophysical model where pattern formation arises from the interplay of myosin contractility and actin turnover. We validate the hypotheses of the model using photobleaching experiments and report that the formation of actin rings is contractility dependent. Moreover, genetic and pharmacological perturbations of the physical properties of the actomyosin gel modify the spacing of the pattern, as the model predicted. In addition, our model posited a role of cortical friction in stabilizing the spacing pattern of actin rings. Consistently, genetic depletion of apical extracellular matrix caused strikingly dynamic movements of actin rings, mirroring our model prediction of a transition from steady to chaotic actin patterns at low cortical friction. Our results therefore demonstrate quantitatively that a hydrodynamical instability of the actin cortex can trigger regular pattern formation and drive morphogenesis in an in vivo setting.

Growth, collapse, and stalling in a mechanical model for neurite motility.

Neurites, the long cellular protrusions that form the routes of the neuronal network, are capable of actively extending during early morphogenesis or regenerating after trauma. To perform this task, they rely on their cytoskeleton for mechanical support. In this paper, we present a three-component active gel model that describes neurites in the three robust mechanical states observed experimentally: collapsed, static, and motile. These states arise from an interplay between the physical forces driven by the growth of the microtubule-rich inner core of the neurite and the acto-myosin contractility of its surrounding cortical membrane. In particular, static states appear as a mechanical balance between traction and compression of these two parallel structures. The model predicts how the response of a neurite to a towing force depends on the force magnitude and recovers the response of neurites to several drug treatments that modulate the cytoskeleton active and passive properties.

One-dimensional collective migration of a proliferating cell monolayer

The importance of collective cellular migration during embryogenesis and tissue repair asks for a sound understanding of underlying principles and mechanisms. Here, we address recent in vitro experiments on cell monolayers, which show that the advancement of the leading edge relies on cell proliferation and protrusive activity at the tissue margin. Within a simple viscoelastic mechanical model amenable to detailed analysis, we identify a key parameter responsible for tissue expansion, and we determine the dependence of the monolayer velocity as a function of measurable rheological parameters. Our results allow us to discuss the effects of pharmacological perturbations on the observed tissue dynamics.

Assembly and positioning of actomyosin rings by contractility and planar cell polarity

The actomyosin cytoskeleton is a primary force-generating mechanism in morphogenesis, thus a robust spatial control of cytoskeletal positioning is essential. In this report, we demonstrate that actomyosin contractility and planar cell polarity (PCP) interact in post-mitotic Ciona notochord cells to self-assemble and reposition actomyosin rings, which play an essential role for cell elongation. Intriguingly, rings always form at the cells′ anterior edge before migrating towards the center as contractility increases, reflecting a novel dynamical property of the cortex. Our drug and genetic manipulations uncover a tug-of-war between contractility, which localizes cortical flows toward the equator and PCP, which tries to reposition them. We develop a simple model of the physical forces underlying this tug-of-war, which quantitatively reproduces our results. We thus propose a quantitative framework for dissecting the relative contribution of contractility and PCP to the self-assembly and repositioning of cytoskeletal structures, which should be applicable to other morphogenetic events. DOI: http://dx.doi.org/10.7554/eLife.09206.001

Rigidity generation by nonthermal fluctuations.

Active stabilization in systems with zero or negative stiffness is an essential element of a wide variety of biological processes. We study a prototypical example of this phenomenon and show how active rigidity, interpreted as a formation of a pseudowell in the effective energy landscape, can be generated in an overdamped stochastic system. We link the transition from negative to positive rigidity with time correlations in the additive noise, and we show that subtle differences in the out-of-equilibrium driving may compromise the emergence of a pseudowell.Active stabilization in systems with zero or negative stiffness is an essential element of a wide variety of biological processes. We study a prototypical example of this phenomenon at a microscale and show how active rigidity, interpreted as a formation of a pseudo-well in the effective energy landscape, can be generated in an overdamped ratchet-type stochastic system. We link the transition from negative to positive rigidity with correlations in the noise and show that subtle differences in out-of-equilibrium driving may compromise the emergence of a pseudo-well.

Cell Locomotion in One Dimension

We overview a sub-class of mathematical models of lamellipodial cell motility on a substrate (crawling) that are based on a projection of a complex intra-cellular dynamics into one dimension. Despite the unavoidable oversimplifications associated with such a representation (loss of flow continuity, neglect of orientational order, misrepresentation of volume control mechanisms, etc.), one-dimensional models are extremely helpful in elucidating the individual roles of the three main active elements of lamellipodial motility: contraction, protrusion and adhesion. Moreover, by shifting the focus from shape to velocity, one-dimensional models reveal in an analytically transparent setting an intricate interplay between these mechanisms involving cooperation and competition.