Capillarity and active cell movement at mesendoderm translocation in the Xenopus gastrula

Abstract

During Xenopus gastrulation, leading edge mesendoderm (LEM) advances animally as wedge-shaped cell mass over the vegetally moving blastocoel roof (BCR). We show that close contact across the BCR-LEM interface correlates with attenuated net advance of the LEM, which is therefore pulled forward by tip cells while the remaining LEM frequently separates from the BCR. Nevertheless, lamellipodia persist on the detached LEM surface. They attach to adjacent LEM cells and depend on PDGF-A, cell surface fibronectin and cadherin. We argue that active cell motility on the LEM surface prevents adverse capillary effects in the liquid LEM tissue as it moves by being pulled. It counters tissue surface tension effects with oriented cell movement and bulges the LEM surface out to keep it close to the curved BCR without attaching to it. Proximity to the BCR is necessary in turn for the maintenance and orientation of lamellipodia that permit mass cell movement with minimal substratum contact. Together with a similar process in epithelial invagination, vertical telescoping, the cell movement at the LEM surface defines a novel type of cell rearrangement, vertical shearing.

Polarized contact behavior in directionally migrating Xenopus gastrula mesendoderm

“…at the front end of leM explants, ephrinb1/ dvl2 activity is required (fig. 7g), and ephrinb1 protein is enriched in a narrow zone at the front of cells (nagel and Winklbauer, 2018;nagel et al, 2021). this suggests a restricted front zone marked by ephrinb1 enrichment and a lateral-back zone, consisting of the remainder of the cell body, where Pak1 is activated (fig.…”

“…in the leM, trains of 2-5 aligned, uniformly oriented cells are seen in the intact embryo in the scanning electron microscope (fig. 7 b,C) (nagel et al, 2004;nagel and Winklbauer, 2018;nagel et al, 2021) or in time lapse recordings of explants where translocating trains form spontaneously on non-oriented substratum (nagel and Winklbauer, 2018). the alignment of interior cells with outward oriented marginal cells in explants also points at Cfl.…”

“…these signaling cascades regulate a complex interplay of protrusion-cell body and cell body-cell body interactions during leM migration (nagel et al, 2021;Huang and Winklbauer, 2018), and in the following we summarize the data in a working model of the system (fig. 7e).…”

“…repeated lateral separation events by repulsion and peeling, combined with persistent maintenance of front-back contacts, could be essential for directional collective cell migration in the embryo. as the leM moves forward on the ectodermal bCr, pulling force is mostly transmitted to the ectoderm through a single row of migrating lead cells at the front of the tissue (Sonavane et al, 2017;nagel et al, 2021) (fig. 7d).…”

“…in leading edge mesendoderm (leM), lamellipodia that attempt to move across the surfaces of adjacent cells are generally induced to detach and collapse, and this contact inhibition of lamellipodia (Cila) is mediated, among other factors like C-cadherin or integrinβ1, by the serine/threonine kinase Pak1 and the eph receptor ligand ephrinb1 (nagel and Winklbauer, 2018). However, as the leM cells move collectively towards the animal pole of the embryo, they extend lamellipodia in the direction of overall movement and underlap each other to form a "shingle arrangement" (Winklbauer and nagel, 1991;nagel et al, 2004, 2009, 2021. this orientation depends on the spatial regulation of lamellipodia collapse by ectodermal Pdgf-a (ataliotis et al, 1995) that is secreted into the extracellular matrix of the substratum.…”