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Requirement for Wnt3 in vertebrate axis formation

Nature Genetics volume 22, pages 361–365 (1999)Cite this article

Abstract

Several studies have implicated Wnt signalling in primary axis formation during vertebrate embryogenesis, yet no Wnt protein has been shown to be essential for this process1,2,3. In the mouse, primitive streak formation is the first overt morphological sign of the anterior-posterior axis. Here we show that Wnt3 is expressed before gastrulation in the proximal epiblast of the egg cylinder, then is restricted to the posterior proximal epiblast and its associated visceral endoderm and subsequently to the primitive streak and mesoderm. Wnt3–/– mice develop a normal egg cylinder but do not form a primitive streak, mesoderm or node. The epiblast continues to proliferate in an undifferentiated state that lacks anterior-posterior neural patterning, but anterior visceral endoderm markers are expressed and correctly positioned. Our results suggest that regional patterning of the visceral endoderm is independent of primitive streak formation, but the subsequent establishment of anterior-posterior neural pattern in the ectoderm is dependent on derivatives of the primitive streak. These studies provide genetic proof for the requirement of Wnt3 in primary axis formation in the mouse.

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Figure 1: Expression pattern of Wnt3 during early mouse development.
Figure 2: Generation of Wnt3–/– mice.
Figure 3: Gross morphological and histological analysis of Wnt3–/– embryos.
Figure 4: Molecular marker analysis of Wnt3 mutants.

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Acknowledgements

We thank S.-L. Ang, T. Gridley, B. Herrmann, B. Hogan, A. Joyner, K. Mahon, H. Schöler, W. Shawlot and D. Wilkinson for in situ hybridization probes; S. Vashnav for histological support; C. Dinh for technical support; and B. Shawlot, P. Tam and C. Wright for helpful comments on the manuscript. This study was supported by a grant from the Human Frontiers Science Program to R.R.B. and from the National Institutes of Health (NCI) to A.B. P.L. was supported by a predoctoral fellowship from the Markey Foundation. M.J.S. was supported by a postdoctoral fellowship from the US Department of Defense.

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Author notes

  1. Pentao Liu

    Present address: Mammalian Genetics Laboratory, ABL-Basic Research Program, P.O. Box B, Building 539, Frederick, Maryland, 21702, USA

  2. Pentao Liu and Maki Wakamiya: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 77030, Texas, USA

    Pentao Liu, Martin J. Shea & Allan Bradley

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

    Maki Wakamiya & Richard R. Behringer

  3. Department of Biochemistry, Baylor College of Medicine, Houston, 77030, Texas, USA

    Urs Albrecht

  4. Howard Hughes Medical Institute, Baylor College of Medicine, Houston, 77030, Texas, USA

    Allan Bradley

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Correspondence to Richard R. Behringer or Allan Bradley.

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Liu, P., Wakamiya, M., Shea, M. et al. Requirement for Wnt3 in vertebrate axis formation. Nat Genet 22, 361–365 (1999). https://doi.org/10.1038/11932

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