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The glial cells missing-1 protein is essential for branching morphogenesis in the chorioallantoic placenta

Nature Genetics volume 25, pages 311–314 (2000)Cite this article

Abstract

Trophoblast cells of the placenta are established at the blastocyst stage and differentiate into specialized subtypes after implantation1,2. In mice, the outer layer of the placenta consists of trophoblast giant cells that invade the uterus and promote maternal blood flow to the implantation site by producing cytokines with angiogenic3 and vasodilatory4 actions. The innermost layer, called the labyrinth, consists of branched villi that provide a large surface area for nutrient transport and are composed of trophoblast cells and underlying mesodermal cells derived from the allantois. The chorioallantoic villi develop after embryonic day (E) 8.5 through extensive folding and branching of an initially flat sheet of trophoblast cells, the chorionic plate, in response to contact with the allantois. We show here that Gcm1, encoding the transcription factor glial cells missing-1 (Gcm1), is expressed in small clusters of chorionic trophoblast cells at the flat chorionic plate stage and at sites of chorioallantoic folding and extension when morphogenesis begins. Mutation of Gcm1 in mice causes a complete block to branching of the chorioallantoic interface, resulting in embryonic mortality by E10 due to the absence of the placental labyrinth. In addition, chorionic trophoblast cells in Gcm1-deficient placentas do not fuse to form syncytiotrophoblast. Abnormal development of placental villi is frequently associated with fetal death and intrauterine growth restriction in humans, and our studies provide the earliest molecular insight into this aspect of placental development.

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Figure 1: Morphogenesis and expression of Gcm1 in mouse placenta during early labryinth development.
Figure 2: Function of Gcm1 in the mouse placenta.
Figure 3: Failure of chorioallantoic placental morphogenesis in Gcm1-deficient embryos.
Figure 4: Failure of syncytiotrophoblast differentiation and tissue morphogenesis, but normal chorionic trophoblast differentiation, in Gcm1-deficient embryos.

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Acknowledgements

We thank Z. Basyuk for providing genomic clones; Y. Lu for histological sections; and A. Bernstein, J. Kingdom and J. Rossant for critical comments on the manuscript. The work was supported by grants from the MRC of Canada (to J.C.C.) and the NIH (to S.J.F. and to R.A.L.).

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Author notes

  1. James C. Cross

    Present address: Department of Biochemistry and Molecular Biology, Genes and Development Research Group, University of Calgary, Calgary, Alberta, Canada

Authors and Affiliations

  1. Program in Development and Fetal Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

    Lynn Anson-Cartwright, Kerri Dawson, Doug Holmyard & James C. Cross

  2. Departments of Anatomy, Stomatology, Pharmaceutical Chemistry, and Obstetrics & Gynecology, University of California, San Francisco, California, USA

    Susan J. Fisher

  3. Brookdale Center for Developmental & Molecular Biology, Mount Sinai School of Medicine, New York, New York, USA

    Robert A. Lazzarini

  4. Department of Obstetrics & Gynaecology, University of Toronto, Toronto, Ontario, Canada

    James C. Cross

  5. Department of Molecular & Medical Genetics, University of Toronto, Toronto, Ontario, Canada

    James C. Cross

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  1. Lynn Anson-Cartwright
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Correspondence to James C. Cross.

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Anson-Cartwright, L., Dawson, K., Holmyard, D. et al. The glial cells missing-1 protein is essential for branching morphogenesis in the chorioallantoic placenta. Nat Genet 25, 311–314 (2000). https://doi.org/10.1038/77076

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