Assembly of a persistent apical actin network by the formin Frl/Fmnl tunes epithelial cell deformability

Abstract

Tissue remodeling during embryogenesis is driven by the apical contractility of the epithelial cell cortex. This behavior arises notably from Rho1/Rok induced transient accumulation of nonmuscle myosin II (MyoII pulses) pulling on actin filaments (F-Actin) of the medio-apical cortex. While recent studies begin to highlight the mechanisms governing the emergence of Rho1/Rok/MyoII pulsatility in different organisms, little is known about how the F-Actin organization influences this process. Focusing on Drosophila ectodermal cells during germband extension and amnioserosa cells during dorsal closure, we show that the medio-apical actomyosin cortex consists of two entangled F-Actin subpopulations. One exhibits pulsatile dynamics of actin polymerization in a Rho1 dependent manner. The other forms a persistent and homogeneous network independent of Rho1. We identify the Frl/Fmnl formin as a critical nucleator of the persistent network since modulating its level, in mutants or by overexpression, decreases or increases the network density. Absence of this network yields sparse connectivity affecting the homogeneous force transmission to the cell boundaries. This reduces the propagation range of contractile forces and results in tissue scale morphogenetic defects. Our work sheds new lights on how the F-Actin cortex offers multiple levels of regulation to affect epithelial cells dynamics..

Coordination of cytoskeletal dynamics and cell behaviour during Drosophila abdominal morphogenesis

“…In large cells, a robust, persistent apicomedial network might be crucial to maintain apical area and transduce contractile forces. In line with our observations, a persistent and a dynamic pool of actin have recently been described in ectodermal cells during germband extension and in amnioserosa cells during dorsal closure in Drosophila, but only the larger amnioserosa cells showed visible actin bundles (Dehapiot et al, 2019).…”

Mechanical competition alters the cellular interpretation of an endogenous genetic programme

“…The former cannot explain single cell stretching in the central mesoderm, while the latter is unlikely given that myosin levels alone predict a wide range of morphogenetic movements in Drosophila 51 A source of this non-linearity may be the actomyosin not assembling in the proper structure. The pulsatile apico-medial actin meshwork needs to be tightly connected to the junctional complexes to function 13,14,42,60,61 relying also on an underlying non-pulsatile actin meshwork 62 . Despite the homogeneous actin meshwork in stretching cells, the areas that are free of active myosin occupy a large proportion of the apical surface -similar to ectodermal or amnioserosa cells in which the connection of pulsatile foci to the underlying actin meshwork is lost 62 .…”

Diversity from similarity: cellular strategies for assigning particular identities to actin filaments and networks

“…This is the case, for example, at the sarcomeres of muscle fibres or at cell–cell junctions in tissues, where the contractile activity of the motors is exerted on actin filaments of opposite polarity [ 30 ]. This is also the case for many disorganized actin networks where myosin activity is capable of driving actin flows or pulsatile phenomena [ 31 – 33 ]. On the contrary, actin filament structures such as filopodia, where the actin filaments all have the same orientation, are not contractile structures [ 4 , 34 ].…”