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Letters to Nature

Nature 404, 95-99 (2 March 2000) | doi:10.1038/35003601; Received 24 September 1999

Eomesodermin is required for mouse trophoblast development and mesoderm formation

Andreas P. Russ1,2,3, Sigrid Wattler4, William H. Colledge2, Samuel A. J. R. Aparicio1,3,6, Mark B. L. Carlton1,2,3, Jonathan J. Pearce1, Sheila C. Barton1, M. Azim Surani1, Kenneth Ryan1, Michael C. Nehls4, Valerie Wilson7 & Martin J. Evans1

  1. Wellcome/CRC Institute for Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK
  2. Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
  3. Paradigm Therapeutics Ltd, Downing Street, Cambridge CB2 3EG, UK
  4. Niedersächsisches Institut für Peptidforschung, Feodor-Lynen-Strasse 31, 30625 Hannover, Germany
  5. Dep. of Oncology, Cambridge Institute of Medical Research, Addenbrookes' Hospital, Cambridge CB2 2XY, UK
  6. Centre of Genome Research, University of Edinburgh, Kings Buildings, West Mains Road, Edinburgh EH9 3JQ, UK
  7. Present addresses: Ingenium Pharmaceuticals AG, Lochhamer Strasse 29, 82152 Martinsried, Germany (S.W.; M.C.N.); Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA (K.R.); Cardiff School of Biosciences, Museum Avenue, PO Box 911, Cardiff CF10 3US, Wales, UK (M.J.E.).

Correspondence to: Andreas P. Russ1,2,3 Correspondence and request for materials should be addressed to A.P.R. (e-mail: Email: apr@mole.bio.cam.ac.uk).

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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 Eomesodermin1 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 cells2. 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.