Mechanical control of notochord morphogenesis by extra-embryonic tissues in mouse embryos

Abstract

Mammalian embryos develop in coordination with extraembryonic tissues, which support embryonic development by implanting embryos into the uterus, supplying nutrition, providing a confined niche, and also providing patterning signals to embryos. Here, we show that in mouse embryos, the expansion of the amniotic cavity (AC), which is formed between embryonic and extraembryonic tissues, provides the mechanical forces required for a type of morphogenetic movement of the notochord known as convergent extension (CE) in which the cells converge to the midline and the tissue elongates along the antero-posterior (AP) axis. The notochord is stretched along the AP axis, and the expansion of the AC is required for CE. Both mathematical modeling and physical simulation showed that a rectangular morphology of the early notochord caused the application of anisotropic force along the AP axis to the notochord through the isotropic expansion of the AC. AC expansion acts upstream of planar cell polarity (PCP) signaling, which regulates CE movement. Our results highlight the importance of extraembryonic tissues as a source of the forces that control the morphogenesis of embryos.

Notochord morphogenesis in mice: Current understanding & open questions

“…Recently, similar movements have also been described during mouse notochord elongation (Yamanaka et al, 2007;Imuta et al, 2014). It was shown that the amniotic cavity provides forces for CE movement necessary for notochord formation, highlighting the importance of extraembryonic tissues as a source of forces to control embryo morphogenesis (Imuta et al, 2014). Additionally, Yamanaka and colleagues used time-lapse imaging to visualize cellular behaviors during notochord formation.…”

Isotropic expansion of external environment induces tissue elongation and collective cell alignment

“…This prompted us to further simplify the situation: instead of an expanding curved three-dimensional surface, we assumed an isotropically expanding two-dimensional plane on which the distance between two arbitrary points increases at a rate proportional to their distance (Fig. 1D; e.g., the distance between two gray circles), as described in our earlier study (13). This situation can also arise in a two-dimensional tissue, like a cell sheet, in which spatially uniform cell proliferation, radial intercalation (16, 17), or cell flattening occurs (Fig.…”

“…1A and B). We showed that in contrast to notochord elongation in other species, which is induced by active cell movement (1, 2, 11), elongation of the mouse notochord is driven, at least in part, by the passive mechanical effects of embryonic expansion (13). Because the expansion of the embryo is almost isotropic, like a spherically expanding balloon, the direction of the extrinsic forces provided from the expanding embryo are expected to be unbiased and uncorrelated with the direction of notochord elongation (Fig.…”

“…Because the expansion of the embryo is almost isotropic, like a spherically expanding balloon, the direction of the extrinsic forces provided from the expanding embryo are expected to be unbiased and uncorrelated with the direction of notochord elongation (Fig. 1B)(13). Furthermore, the cells are also elongated in a direction parallel to that of notochord elongation (Fig.…”

“…The width of the notochord decreases, so the tissue must elongate. Images were adapted from Imuta et al (13). B) Schematic illustration of a cell cluster or tissue on an expanding sphere.…”