Integrin β1 coordinates survival and morphogenesis of the embryonic lineage upon implantation and pluripotency transition

Cell Rep. 2021 Mar 9;34(10):108834. doi: 10.1016/j.celrep.2021.108834.


At implantation, the embryo establishes contacts with the maternal endometrium. This stage is associated with a high incidence of preclinical pregnancy losses. While the maternal factors underlying uterine receptivity have been investigated, the signals required by the embryo for successful peri-implantation development remain elusive. To explore these, we studied integrin β1 signaling, as embryos deficient for this receptor degenerate at implantation. We demonstrate that the coordinated action of pro-survival signals and localized actomyosin suppression via integrin β1 permits the development of the embryo beyond implantation. Failure of either process leads to developmental arrest and apoptosis. Pharmacological stimulation through fibroblast growth factor 2 (FGF2) and insulin-like growth factor 1 (IGF1), coupled with ROCK-mediated actomyosin inhibition, rescues the deficiency of integrin β1, promoting progression to post-implantation stages. Mutual exclusion between integrin β1 and actomyosin seems to be conserved in the human embryo, suggesting the possibility that these mechanisms could also underlie the transition of the human epiblast from pre- to post-implantation.

Keywords: actomyosin; apoptosis; epiblast; human embryo; integrins; morphogenesis; mouse embryo; survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / metabolism
  • Amides / pharmacology
  • Animals
  • Embryo Implantation
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / metabolism
  • Embryonic Development
  • Female
  • Fibroblast Growth Factor 2 / pharmacology
  • Germ Layers / growth & development
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 / metabolism
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Morphogenesis* / drug effects
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism
  • Pyridines / pharmacology
  • Signal Transduction
  • rho-Associated Kinases / antagonists & inhibitors
  • rho-Associated Kinases / metabolism


  • Amides
  • Integrin beta1
  • Pyridines
  • Fibroblast Growth Factor 2
  • Y 27632
  • Insulin-Like Growth Factor I
  • Actomyosin
  • rho-Associated Kinases
  • Glycogen Synthase Kinase 3