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Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo

Nature volume 428, pages 387–392 (2004)Cite this article

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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Figure 1: Asymmetric expression of Lefty1 and Cerl before DVE migration.
Figure 2: Ectopic expression of Lefty1 or Cerl directs DVE migration.
Figure 3: Patterns of VE cell proliferation in wild-type and various mutant embryos.
Figure 4: Nodal antagonists inhibit and Nodal promotes VE cell proliferation.
Figure 5: Anteroposterior patterning defects in the absence of Lefty1 and Cerl.

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Acknowledgements

We thank E. Robertson for NodallacZ mutant mice; R. Beddington for the Hex probe; V. Gallo for expression vectors for Cdk and dominant negative Cdk; and N. Mine and Y. Ohnishi for help in improving the lipofection procedure. We also thank S. Srinivas for exchanging unpublished data. This work was supported by grants from the Ministry of Education, Science, Sports, and Culture of Japan (to C.M. and H.H.), a grant from CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation (to H.H.), a grant from the NIH (to R.R.B.), and a grant from the Association pour la Recherche sur le Cancer and by funds from the INSERM, the CNRS and the Hopital Universitaire de Strasbourg (to S.-L.A.). M.Y. is a recipient of a fellowship from the Japan Society for the Promotion of Science for Japanese Junior Scientists.

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Author notes

  1. Aitana Perea-Gomez

    Present address: Institut Jacques Monod, CNRS, Universités Paris 6 et 7, 75251, Paris Cedex, 05, France

  2. William Shawlot

    Present address: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, 55455, USA

Authors and Affiliations

  1. Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST), 1-3 Yamada-oka, Suita, 565-0871, Osaka, Japan

    Masamichi Yamamoto, Yukio Saijoh, Hiroshi Hamada & Chikara Meno

  2. IGBMC/CNRS/INSERM, Université Louis Pasteur, 67404 Illkirch Cedex, CU de Strasbourg, France

    Aitana Perea-Gomez & Siew-Lan Ang

  3. Department of Molecular Genetics, M.D. Anderson Cancer Center, University of Texas, Houston, Texas, 77030, USA

    William Shawlot & Richard R. Behringer

  4. Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, NW7 1AA, London, UK

    Siew-Lan Ang

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Correspondence to Hiroshi Hamada.

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Supplementary information

Supplementary Information

Includes supplementary figure legends and supplementary methods. (DOC 52 kb)

Supplementary Figure 1

Delayed migration of the DVE in FoxH1 mutant embryos. (PDF 213 kb)

Supplementary Figure 2

Nodal expression in FoxH1 mutant embryos. (PDF 856 kb)

Supplementary Figure 3

(see full legend) (PDF 1372 kb)

Supplementary Figure 4

Model for A-P determination by Nodal antagonists. (PDF 257 kb)

Supplementary Figure 5

Introduction of a lacZ-expression vector by lipofection. (PDF 173 kb)

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Yamamoto, M., Saijoh, Y., Perea-Gomez, A. et al. Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo. Nature 428, 387–392 (2004). https://doi.org/10.1038/nature02418

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