Convergent extension requires adhesion-dependent biomechanical integration of cell crawling and junction contraction

Abstract

Convergent extension is an evolutionarily conserved collective cell movement that elongates the body axis of all animals and is required for the morphogenesis of several organ systems. Decades of study have revealed two distinct mechanisms of cell movement during CE, one based on cell crawling and the other on junction contraction. How these two behaviors collaborate during CE is unknown. Here, using quantitative live cell imaging we show that these two modes act both independently and in concert during CE, but that cell movement is more effective when the two modes are simultaneously integrated. Based on these findings, we developed a novel computational model that for the first time treats crawling and contraction independently. This model not only confirmed the biomechanical efficacy of integrating the two modes but also revealed for the first time how the two modes are affected by cell adhesion. Prompted by our modeling, we show that disruption of cell adhesion by knockdown of the Arvcf catenin results in specific failure of integration of crawling with contraction. These data are significant for providing new biomechanical and cell biological insights into a fundamental morphogenetic process implicated in human neural tube defects and skeletal dysplasias.

Cell adhesions link subcellular actomyosin dynamics to tissue scale force production during vertebrate convergent extension

“…Strikingly, mosaic labelling experiments in that paper suggest that the dampened amplitude of actin oscillations following Arvcf-Kd shown here (Fig. 6) result largely from a specific effect of Arvcf on the mediolateral protrusions (Weng et al, 2021). This result is interesting: On the one hand, it is consistent with the previous finding that Arvcf is required for normal Rac activation during Xenopus CE (Fang et al, 2004), and Rac is generally considered to be essential for lamellipodial protrusions (Nobes and Hall, 1995).…”

“…CE in epithelial cells in both mice and Drosophila is driven by the combined action of basally positioned cell crawling via mediolaterally-positioned protrusions and contraction of apically positioned anteroposterior cell-cell junctions (Huebner and Wallingford, 2018;Sun et al, 2017;Williams et al, 2014). We have now shown that these two modes of intercalation are not physically separated and work in tandem in mesenchymal cells of the Xenopus gastrula (Weng et al, 2021). We further show that the integration of the two modes is crucial for high efficiency of cell intercalation.…”

“…In this light, data from our companion paper provides key insights (see (Weng et al, 2021). CE in epithelial cells in both mice and Drosophila is driven by the combined action of basally positioned cell crawling via mediolaterally-positioned protrusions and contraction of apically positioned anteroposterior cell-cell junctions (Huebner and Wallingford, 2018;Sun et al, 2017;Williams et al, 2014).…”

“…1C, E), though extensive actin-based protrusions between neighboring cells at these deep cell-cell interfaces are also observed (Green and Davidson, 2007;; Cdh3 localizes to dynamic foci at deeper cell-cell interfaces (Fagotto et al, 2013;Huebner et al, 2021). Because of the key role of these deeper cell-cell interfaces in CE (Huebner et al, 2021;Shindo et al, 2019;Shindo and Wallingford, 2014;Weng et al, 2021), we used live imaging to identify Cdh3-interacting proteins that localize to these sites.…”

Mechanical heterogeneity along single cell-cell junctions is driven by lateral clustering of cadherins during vertebrate axis elongation

“…In epithelial cells, contraction occurs apically, while cell crawling acts basolaterally ( Sun et al, 2017 ; Williams et al, 2014 ). In Xenopus mesenchymal cells, which lack apical-basal polarity, we have found that the two mechanisms are integrated, driving more effective intercalation when both mechanisms act simultaneously ( Weng et al, 2021 ). Another key challenge, therefore, will be to ask how the asymmetry of Cdh3 clustering observed here relates to contraction and/or cell crawling-based intercalation.…”