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

Abstract

Tissue morphogenesis requires the control of physical forces by molecular patterning systems encoded in the genome. For example, tissue-level mechanical transformations in vertebrate embryos require the activity of cadherin adhesion proteins and the Planar Cell Polarity (PCP) signaling system. At the tissue level, collective cell movements are known to be highly complex, displaying combinations of fluid/solid behaviors, jamming transitions, and glass-like dynamics. The sub-cellular origin of these heterogeneous tissue dynamics is undefined. Here, high-speed super-resolution imaging and physical methods for quantifying motion revealed that the subcellular behaviors underlying vertebrate embryonic axis elongation display glass-like dynamic heterogeneities. A combination of theory and experiment demonstrates these behaviors are highly local, displaying asymmetries even within individual cell-cell junctions. Moreover, we demonstrate that these mechanical asymmetries require patterned lateral (cis-) clustering of cadherins that is dependent upon PCP signaling. These findings illuminate the mechanisms by which defined molecular patterning systems tune the mechanics of sub-cellular behaviors that drive vertebrate axis elongation. Introduction:

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

“…(Levayer and Lecuit, 2013;Truong Quang et al, 2013), the role of cadherin adhesion in vertebrate gastrulation is only poorly understood. Recent suggest a key role in both crawling-and contraction-based intercalation (Huebner et al, 2020;Pfister et al, 2016), but our work here further demonstrates that fine-tuning of adhesion is crucial for the integration of the two, which is itself essential for normal morphogenesis. Further exploration of cadherin adhesion and its role in integrating biomechanical forces that drive CE will be important.…”

The Wnt/PCP formin Daam1 drives cell-cell adhesion during nephron development

“…Second, we show that Daam1 localizes to actin protrusions and newly formed cell-cell contacts in developing nephrons, suggesting that Daam1 coordinates assembly of cell junctions during CE via E-cadherin. Actin polymerization at the cell membrane mediates polarized movement and intercalation of cells during CE through cadherin engagement (Huebner and Wallingford, 2018;Huebner et al, 2020). Here we show that Daam1 functions to ensure proper organization and size of the nephric primordium at the time of CE and polarized movement of renal epithelial sheets.…”

Cell-Cell Adhesion During Nephron Development Is Driven by Wnt/PCP Formin Daam1

“…Second, we show that Daam1 localizes to actin protrusions and newly formed cell-cell contacts in developing nephron, suggesting that Daam1 via E-cadherin coordinates the assembly of cellcell junctions during CE. Actin polymerization at the cell's membrane mediates polarized movement and intercalation of cells during CE through engagement of cadherins (Huebner and Wallingford, 2018;Huebner et al, 2020). Here, we show that Daam1 activity functions to ensure proper organization and size of nephrogenic primordium at the time of CE as well as polarized movement of renal epithelial sheets.…”