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Nodal signalling in the epiblast patterns the early mouse embryo

Nature volume 411, pages 965–969 (2001)Cite this article

Abstract

Shortly after implantation the mouse embryo comprises three tissue layers. The founder tissue of the embryo proper, the epiblast, forms a radially symmetric cup of epithelial cells that grows in close apposition to the extra-embryonic ectoderm and the visceral endoderm. This simple cylindrical structure exhibits a distinct molecular pattern along its proximal–distal axis1. The anterior–posterior axis of the embryo is positioned later by coordinated cell movements that rotate the pre-existing proximal–distal axis2,3,4,5. The transforming growth factor-β family member Nodal is known to be required for formation of the anterior–posterior axis6. Here we show that signals from the epiblast are responsible for the initiation of proximal–distal polarity. Nodal acts to promote posterior cell fates in the epiblast and to maintain molecular pattern in the adjacent extra-embryonic ectoderm. Both of these functions are independent of Smad2. Moreover, Nodal signals from the epiblast also pattern the visceral endoderm by activating the Smad2-dependent pathway required for specification of anterior identity in overlying epiblast cells. Our experiments show that proximal–distal and subsequent anterior–posterior polarity of the pregastrulation embryo result from reciprocal cell–cell interactions between the epiblast and the two extra-embryonic tissues.

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Figure 1: Distinct patterning defects exhibited by epiblast tissue deficient in Nodal or Smad2.
Figure 2: Visceral endoderm deficient in Nodal or Smad2 lacks anterior identity.
Figure 3: Tissue-specific Smad2-dependent and -independent signals regulate Nodal activities in the early embryo.
Figure 4: Temporally and spatially distinct Nodal activities pattern the anterior–posterior (A↔P) axis.

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Acknowledgements

We thank E. Bikoff, P. Hoodless, R. Dunn and K. Tremblay for helpful discussions and comments on the manuscript; J. Wrana and P. Hoodless for permission to cite unpublished work; and P. Lewko and J. Rocca for animal care. This work was funded by the NIH and supported by a postdoctoral fellowship from the Wellcome Trust (J.B.) and a Charles A. King Trust fellowship (D.P.N.). This paper is dedicated to the memory of Rosa Beddington, our dear friend and colleague, who died on 18 May 2001.

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, 02138, Massachusetts, USA

    Jane Brennan, Cindy C. Lu, Dominic P. Norris & Elizabeth J. Robertson

  2. Division of Mammalian Development, National Institute for Medical Research, The Ridgeway, London, NW7 1AA, UK

    Tristan A. Rodriguez & Rosa S. P. Beddington

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  1. Jane Brennan
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  4. Tristan A. Rodriguez
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  5. Rosa S. P. Beddington
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Corresponding author

Correspondence to Elizabeth J. Robertson.

Supplementary Information

Figure 1

(JPG 502 KB)

Nodal deficient embryos contain abundant extra-embryonic ectoderm. Whole mount in situ hybridisation (a-d) and bgal (e, f) analysis of early gastrulation control (c, e) or Nodal mutant (a, b, d, e) embryos. L1416 is expressed in the extra-embryonic ectoderm of Nodal mutants (a). Red line indicates plane of section shown in b. Longitudinal sections taken through 6.5dpc embryos (c-f). Otx2 was used to clearly differentiate the epiblast, which expresses Otx2 (c), from the extra-embryonic ectoderm (outlined with dotted line). In the Nodal mutant (d) the extra-embryonic ectoderm is clearly a distinct tissue population from the epiblast (outlined with dotted line). Similarly, the NodallacZ allele was used to mark the distal epiblast (e), adjacent to this tissue is the extra-embryonic ectoderm (e, f).

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Brennan, J., Lu, C., Norris, D. et al. Nodal signalling in the epiblast patterns the early mouse embryo. Nature 411, 965–969 (2001). https://doi.org/10.1038/35082103

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