During development, tissues evolve into complex entities by combining different types of specialized cells. To create this complex ensemble, precursor cells move between neighbors to reach the ideal position to perform their function. Our work aims to understand the molecular and cellular mechanisms required for the intercalation of specialized cell precursors in the mucociliary epithelium of Xenopus embryos using quantitative dynamic imaging and biophysical methods. Here we describe that intercalation of novel multi-cell precursors (MCCs) is directed by filopodia to the tricellular junctions (TCJs) of overlying epithelial cells. Furthermore, precursor intercalation is dependent on the activity of the lipolysis-stimulated lipoprotein receptor (LSR) protein, suggesting novel undefined roles for LSR in cell movement. To complement our in vivo findings, we designed a theoretical framework that models the physical environment of the mucociliary epithelium. Our model shows that MCC precursors probe the local stiffness of the overlying tissue by using filopodia to pull on TCJs, which then directs cell movement. Overall, our work defines a novel durotaxis-like mechanism that leads to the intercalation of MCC precursors into the developing vertebrate epithelium.
Apical emergence of a multi-ciliated cell (MCC) within the epidermis of Xenopus laevis (green - MCC progenitor, magenta - goblet cells)