1. Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST), 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan
2. IGBMC/CNRS/INSERM, Université Louis Pasteur, 67404 Illkirch Cedex, CU de Strasbourg, France
3. Department of Molecular Genetics, M.D. Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA
4. Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
5. Present addresses: Institut Jacques Monod, CNRS, Universités Paris 6 et 7, 75251 Paris Cedex 05, France (A.P.-G.); Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA (W.S.)

Correspondence to: Hiroshi Hamada¹ Email: hamada@fbs.osaka-u.ac.jp

Abstract

Patterning of the mouse embryo along the anteroposterior axis during body plan development requires migration of the distal visceral endoderm (DVE) towards the future anterior side by a mechanism that has remained unknown. Here we show that Nodal signalling and the regionalization of its antagonists are required for normal migration of the DVE. Whereas Nodal signalling provides the driving force for DVE migration by stimulating the proliferation of visceral endoderm cells, the antagonists Lefty1 and Cerl determine the direction of migration by asymmetrically inhibiting Nodal activity on the future anterior side.

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