Basement membrane remodelling regulates mouse embryogenesis

Nature. 2020 Jun;582(7811):253-258. doi: 10.1038/s41586-020-2264-2. Epub 2020 May 6.

Abstract

Tissue sculpting during development has been attributed mainly to cellular events through processes such as convergent extension or apical constriction1,2. However, recent work has revealed roles for basement membrane remodelling in global tissue morphogenesis3-5. Upon implantation, the epiblast and extraembryonic ectoderm of the mouse embryo become enveloped by a basement membrane. Signalling between the basement membrane and these tissues is critical for cell polarization and the ensuing morphogenesis6,7. However, the mechanical role of the basement membrane in 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 the expression of matrix metalloproteinases. This basement membrane remodelling facilitates embryo growth before gastrulation. The establishment of the anterior-posterior axis8,9 further regulates basement membrane remodelling by localizing Nodal signalling-and therefore the 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 basement membrane of the prospective primitive streak more prone to breaching. Thus spatiotemporally regulated basement membrane remodelling contributes to the coordination of embryo growth, morphogenesis and gastrulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basement Membrane / cytology
  • Basement Membrane / embryology*
  • Basement Membrane / metabolism*
  • Blastocyst / cytology
  • Blastocyst / metabolism
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / embryology*
  • Embryo, Mammalian / metabolism*
  • Embryonic Development*
  • Extracellular Matrix / metabolism
  • Female
  • Gastrula / embryology
  • Male
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Nodal Signaling Ligands / metabolism
  • Primitive Streak / cytology
  • Primitive Streak / embryology
  • Primitive Streak / metabolism

Substances

  • Nodal Signaling Ligands
  • Matrix Metalloproteinases