Biology subjects

Lecuit, T.

Publications and source records attributed to Lecuit, T..

3 recordsLinked to original sources

bioRxiv2018

Transcriptional initiation and mechanically driven self-propagation of a tissue contractile wave during axis elongation

Tissue morphogenesis emerges from coordinated cell shape changes driven by actomyosin contraction1, 2. Spatial patterns of gene expression regionalize and polarize cell behaviours, such as apical constriction in the ventral mesoderm and cell intercalation in the lateral ectoderm of Drosophila3. Thus, tissue dynamics is largely governed genetically. Actomyosin contractile networks drive cell and tissue-level shape changes and can respond to mechanical stimuli 4-9. However how genetic information and mechanical control drive tissue-level morphogenesis is not well understood. Here we report two phases and modalities of Rho1 and non-muscle MyosinII (MyoII) activation in the Drosophila posterior endoderm. First, Rho1/MyoII are induced apically in a spatially restricted primordium region via localized transcription of the GPCR ligand Fog. Second, a tissue-scale travelling wave of Rho1/MyoII activation and cell invagination progresses anteriorly across the dorsal epithelium at a constant speed of 1 cell every 3 minutes. Remarkably, the MyoII wave does not require sustained gene transcription, and is also insensitive to perturbations in the level and pattern of Fog expression. Thus, while fog transcription initiates Rho1/MyoII activation in the primordium, Fog delivery does not govern wave dynamics. Instead, perturbing the mechanical environment of the endoderm impaired MyoII wave dynamics. MyoII inhibition blocked acute Rho1 activation and propagation, suggesting that MyoII contractility provides both local feedback amplification and spatial coupling necessary for wave progression. Finally, we identify a cycle of 3D cell deformations that link MyoII activation and invagination in one row of cells to vitelline membrane attachment, apical spreading, MyoII activation and invagination in the next row, to drive anterior progression of the invagination wave. Thus endoderm morphogenesis emerges from local transcriptional initiation and a mechanically driven travelling cycle of cell contraction and deformation.

developmental biology↗

bioRxiv2018

Two contractile pools of actomyosin distinctly load and tune E-cadherin levels during morphogenesis

During epithelial morphogenesis, cell contacts (junctions) are constantly remodeled by mechanical forces that work against adhesive forces. E-cadherin complexes play a pivotal role in this process by providing persistent cell adhesion and by transmitting mechanical tension. In this context, it is unclear how mechanical forces affect E-cadherin adhesion and junction dynamics.\n\nDuring Drosophila embryo axis elongation, Myosin-II activity in the apico-medial and junctional cortex generates mechanical forces to drive junction remodeling. Here we report that the ratio between Vinculin and E-cadherin intensities acts as a ratiometric readout for these mechanical forces (load) at E-cadherin complexes. Medial Myosin-II loads E-cadherin complexes on all junctions, exerts tensile forces, and increases levels of E-cadherin. Junctional Myosin-II, on the other hand, biases the distribution of load between junctions of the same cell, exerts shear forces, and decreases the levels of E-cadherin. This work suggests distinct effects of tensile versus shear stresses on E-cadherin adhesion.

cell biology↗

bioRxiv2017

Viscoelastic dissipation stabilizes cell shape changes during tissue morphogenesis

Tissue morphogenesis relies on the production of active cellular forces. Understanding how such forces are mechanically converted into cell shape changes is essential to our understanding of morphogenesis. Here we use Myosin II pulsatile activity during Drosophila embryogenesis to study how transient forces generate irreversible cell shape changes. Analyzing the dynamics of junction shortening and elongation resulting from Myosin II pulses, we find that long pulses yield less reversible deformations, typically a signature of dissipative mechanics. This is consistent with a simple viscoelastic description, which we use to model individual shortening and elongation events. The model predicts that dissipation typically occurs on the minute timescale, a timescale commensurate with that of force generation by Myosin II pulses. We test this estimate by applying time-controlled forces on junctions with optical tweezers. Our results argue that active junctional deformation is stabilized by dissipation. Hence, tissue morphogenesis requires coordination between force generation and dissipation.

developmental biology↗