Mechanics of cell integration in vivo

TL;DR

This study uncovers how mechanical forces and cellular protrusions facilitate cell integration into tissues during development, revealing new roles for specific proteins and physical interactions at the cell-tissue interface.

Contribution

It introduces a novel understanding of mechanical interplay and identifies LSR's role in filopodia dynamics during cell integration in vivo.

Findings

Filopodia probe tissue stiffness to guide cell positioning.

LSR is essential for filopodia function and cell intercalation.

Mechanical forces remodel epithelial junctions to aid cell integration.

Abstract

During embryonic development, regeneration and homeostasis, cells have to physically integrate into their target tissues, where they ultimately execute their function. Despite a significant body of research on how mechanical forces instruct cellular behaviors within the plane of an epithelium, very little is known about the mechanical interplay at the interface between migrating cells and their surrounding tissue, which has its own dynamics, architecture and identity. Here, using quantitative in vivo imaging and molecular perturbations, together with a theoretical model, we reveal that multiciliated cell (MCC) precursors in the Xenopus embryo form dynamic filopodia that pull at the vertices of the overlying epithelial sheet to probe their stiffness and identify the preferred positions for their integration into the tissue. Moreover, we report a novel function for a structural component of vertices, the lipolysis-stimulated lipoprotein receptor (LSR), in filopodia dynamics and show its critical role in cell intercalation. Remarkably, we find that pulling forces equip the MCCs to remodel the epithelial junctions of the neighboring tissue, enabling them to generate a permissive environment for their integration. Our findings reveal the intricate physical crosstalk at the cell-tissue interface and uncover previously unknown functions for mechanical forces in orchestrating cell integration.