Basement membrane remodelling regulates mouse embryogenesis

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.