Basement membrane remodelling regulates mouse embryogenesis

Abstract

Tissue sculpting during development has been attributed mainly to cellular events through processes such as convergent extension or apical constriction 1 , 2 . Recent work, however, has revealed roles for basement membrane remodelling in global tissue morphogenesis 3 – 5 . Upon implantation, the epiblast and extra-embryonic ectoderm of the mouse embryo become enveloped with a basement membrane. Signalling between the basement membrane and these tissues is critical for cell polarization and the ensuing morphogenesis 6 , 7 . However, the mechanical role of the basement membrane for post-implantation embryogenesis remains unknown. Here, we demonstrate the importance of spatiotemporally regulated basement membrane remodelling during early embryonic development. Specifically, we show that Nodal signalling directs the generation and dynamic distribution of perforations in the basement membrane by regulating expression of matrix metalloproteinases. This basement membrane remodelling facilitates embryo growth before gastrulation. The establishment of the anterior-posterior axis 8 , 9 further regulates basement membrane remodelling by localizing Nodal signalling, and therefore activity of matrix metalloproteinases and basement-membrane perforations, to the posterior side of the embryo. Perforations on the posterior side are essential for primitive streak extension during gastrulation by rendering the prospective primitive streak’s basement membrane more prone to breaching. Thus spatio-temporally regulated basement membrane remodelling contributes to the coordination of embryo growth, morphogenesis and gastrulation.

Material-mediated histogenesis using mechano-chemically microstructured cell niches

“…This observation suggests a novel role of niche mechanics in cell-fate choices and the spatial variations in the mechanical property of the niche may underpin the patterning of tissues. These findings are consistent with the notion that protease softening of the basement membrane material plays a role in the patterning of tissues in the anterior-posterior axis of the embryo 49 . Thus, engineering niche microstructures provides an entry point to better understand the mechanisms that underpin spatial patterning of germ layer tissues in stem cell-based embryoid models.…”

“…To highlight the novelty and utility of these niches, we focused our research on studying a phenomenon that would otherwise be impossible to explore using alternative tools. We choose to research the role of matrix softening known to drive germ-layer formation and regionalization of tissues in the avian and murine embryos 47,48 . Using voxelated niches, we investigated if a similar process may exist in humans.…”

Inducible Stem-Cell-Derived Embryos Capture Mouse Morphogenetic Events In Vitro

“…The PS of iETX embryos expressed higher levels of Bry (Figure 5H), which was accompanied by downregulation of E-cadherin and upregulation of N-cadherin (Figure 5H). Finally, egressed cells co-expressed Bry and the EMT marker Snail (Fig- ure 5I), suggesting that gastrulation in iETX embryos follows the same process as the natural embryo (Ramkumar et al, 2016;Punovuori et al, 2019;Kyprianou et al, 2020). Based on Snail-YFP expression, 64% of the structures were undergoing EMT at day 5 (27/42, see also Figure S5D).…”

“…Nodal Inhibitory Treatment iETX embryos were collected at day 4 and incubated in SB431542 (STEMCELL Technologies 72234) for 24 hours at a concentration of 10 mM (Kyprianou et al, 2020). Following Nodal inhibitor treatment, they were fixed and processed for immunofluorescence (below).…”

Mouse embryonic stem cells switch migratory behaviour during early differentiation

“…This is in part due to the difficulty of investigating individual cell behaviour in mammalian embryos. Yet, recent studies highlight the importance of changes in cellular properties, such as cell surface tension, adhesiveness, and extracellular matrix interactions, during early mouse development (Kyprianou et al, 2020, Samarage et al, 2015, Maitre et al, 2015.…”