Integrin β1 coordinates survival and morphogenesis of the embryonic lineage upon implantation and pluripotency transition
Matteo Amitaba Molè,
Antonia Weberling,
Reinhard Fässler,
Alison Campbell,
Simon Fishel,
Magdalena Zernicka-Goetz
Affiliations
Matteo Amitaba Molè
Mammalian Embryo and Stem Cell Group, Department of Physiology, Development, and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
Antonia Weberling
Mammalian Embryo and Stem Cell Group, Department of Physiology, Development, and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
Reinhard Fässler
Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
Alison Campbell
CARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham NG8 6PZ, UK
Simon Fishel
CARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham NG8 6PZ, UK; School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, UK
Magdalena Zernicka-Goetz
Mammalian Embryo and Stem Cell Group, Department of Physiology, Development, and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK; Plasticity and Self-Organization Group, Division of Biology and Biological Engineering, California Institute of Technology (Caltech), Pasadena, CA 91125, USA; Corresponding author
Summary: 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.
