Eomesodermin is required for mouse trophoblast development and mesoderm formation

The earliest cell fate decision in the mammalian embryo separates the extra-embryonic trophoblast lineage, which forms the fetal portion of the placenta, from the embryonic cell lineages. The body plan of the embryo proper is established only later at gastrulation, when the pluripotent epiblast gives rise to the germ layers ectoderm, mesoderm and endoderm. Here we show that the T-box gene Eomesodermin 1 performs essential functions in both trophoblast development and gastrulation. Mouse embryos lacking Eomesodermin arrest at the blastocyst stage. Mutant trophoectoderm does not differentiate into trophoblast, indicating that Eomesodermin may be required for the development of trophoblast stem cells 2 . In the embryo proper, Eomesodermin is essential for mesoderm formation. Although the specification of the anterior–posterior axis and the initial response to mesoderm-inducing signals is intact in mutant epiblasts, the prospective mesodermal cells are not recruited into the primitive streak. Our results indicate that Eomesodermin defines a conserved molecular pathway controlling the morphogenetic movements of germ layer formation and has acquired a new function in mammals in the differentiation of trophoblast.

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Acknowledgements

We thank J. Gurdon, A. Bulfone, A. Zorn, N. Papalopulu, D. St. Johnston and R. Pedersen for discussion; X. Sun and F. Beck for communicating results before publication; G. Martin, C. Wright and R. Milner for gifts of probes and reagents; F. Wianny and A. Sossick for help with confocal microscopy; J. Wilson for technical assistance; J. Ferguson, P. Whiting and R. Plumridge for animal care. A.P.R. thanks W. Gross for continuing support and advice. This work was funded by grants from the Wellcome Trust. V.W. is supported by a Medical Research Council Career Development Award.

Author information

  1. Sigrid Wattler & Michael C. Nehls Present address: Ingenium Pharmaceuticals AG, Lochhamer Strasse 29, 82152, Martinsried, Germany
  2. Kenneth Ryan Present address: Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA
  3. Martin J. Evans Present address: Cardiff School of Biosciences, Museum Avenue, PO Box 911, Cardiff, CF10 3US, Wales, UK

Authors and Affiliations

  1. Wellcome/CRC Institute for Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, UK Andreas P. Russ, Samuel A. J. R. Aparicio, Mark B. L. Carlton, Jonathan J. Pearce, Sheila C. Barton, M. Azim Surani, Kenneth Ryan & Martin J. Evans
  2. Department of Physiology, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK Andreas P. Russ, William H. Colledge & Mark B. L. Carlton
  3. Paradigm Therapeutics Ltd, Downing Street, Cambridge, CB2 3EG, UK Andreas P. Russ, Samuel A. J. R. Aparicio & Mark B. L. Carlton
  4. Niedersächsisches Institut für Peptidforschung, Feodor-Lynen-Strasse 31, Hannover, 30625 , Germany Sigrid Wattler & Michael C. Nehls
  5. Dep. of Oncology, Cambridge Institute of Medical Research, Addenbrookes' Hospital, Cambridge, CB2 2XY, UK Samuel A. J. R. Aparicio
  6. Centre of Genome Research, University of Edinburgh, Kings Buildings, West Mains Road, Edinburgh, EH9 3JQ, UK Valerie Wilson
  1. Andreas P. Russ