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The amnionless gene, essential for mouse gastrulation, encodes a visceral-endoderm–specific protein with an extracellular cysteine-rich domain

Nature Genetics volume 27, pages 412–416 (2001)Cite this article

Abstract

Fate-mapping experiments in the mouse have revealed that the primitive streak can be divided into three functional regions1: the proximal region gives rise to germ cells and the extra-embryonic mesoderm of the yolk sac; the distal region generates cardiac mesoderm and node-derived axial mesendoderm; and the middle streak region produces the paraxial, intermediate and lateral plate mesoderm of the trunk. To gain insight into the mechanisms that mediate the assembly of the primitive streak into these functional regions, we have cloned and functionally identified the gene disrupted in the amnionless (amn) mouse, which has a recessive, embryonic lethal mutation that interferes specifically with the formation and/or specification of the middle primitive streak region during gastrulation2. Here we report that the gene Amn encodes a novel type I transmembrane protein that is expressed exclusively in the extra-embryonic visceral endoderm layer during gastrulation. The extracellular region of the Amn protein contains a cysteine-rich domain with similarity to bone morphogenetic protein (BMP)-binding cysteine-rich domains in chordin, its Drosophila melanogaster homolog (Short gastrulation) and procollagen IIA (ref. 3). Our findings indicate that Amn may direct the production of trunk mesoderm derived from the middle streak by acting in the underlying visceral endoderm to modulate a BMP signaling pathway.

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Figure 1: The amn locus harbors a small DNA deletion.
Figure 2: The BAC80 transgene rescues the amn phenotype.
Figure 3: Identification of an Amn candidate that is disrupted and partially deleted by the transgene insertion.
Figure 4: Targeted deletion of Amn candidate recapitulates the amn phenotype.
Figure 5: Amn is expressed exclusively in primitive endoderm and visceral endoderm during early postimplantation stages.
Figure 6: Amn encodes a cysteine-rich (CR) region with homology to CR2 in chordin.

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Acknowledgements

We thank K. Anderson, L. Niswander, P. Wilson, C. Blobel and F. Costantini for discussions and critical reading of the manuscript; J.-H. Dong, J. Ingenito, R. Lester and W. Mark for technical expertise and advice; Y. Zhang and M. Grunwald for technical assistance; J. Choi for his contribution to database analyses; R. Rivi and F. Lupu for discussions and critical reading of the manuscript; and R. Yeung for assistance in the generation of the Amn polyclonal antisera. This work was supported by NIH grant GM58726 (E.L.) and the MSKCC Support Grant CA-08748.

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  1. Sundeep Kalantry and Sharon Manning: These authors contributed equally to this work.

Authors and Affiliations

  1. Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, Weill Graduate School of Medical Sciences of Cornell University, New York, New York, USA

    Sundeep Kalantry, Sharon Manning, Olivia Haub, Carol Tomihara-Newberger, Hong-Gee Lee, Katia Manova & Elizabeth Lacy

  2. Molecular Biology Graduate Program, Weill Graduate School of Medical Sciences of Cornell University, New York, New York, USA

    Sundeep Kalantry, Sharon Manning, Carol Tomihara-Newberger & Elizabeth Lacy

  3. Department of Pathology, Box 357470, University of Washington, Seattle, Washington, USA

    Jennifer Fangman & Christine M. Disteche

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  1. Sundeep Kalantry
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Correspondence to Elizabeth Lacy.

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Kalantry, S., Manning, S., Haub, O. et al. The amnionless gene, essential for mouse gastrulation, encodes a visceral-endoderm–specific protein with an extracellular cysteine-rich domain. Nat Genet 27, 412–416 (2001). https://doi.org/10.1038/86912

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