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Esx1 is an X-chromosome-imprinted regulator of placental development and fetal growth

Nature Genetics volume 20, pages 309–311 (1998)Cite this article

Abstract

In marsupials and mice, the paternally derived X chromosome is preferentially inactivated in the placental tissues of female embryos1,2,3,4. We show here that the X-linked homeobox gene Esx1 (Refs 5,6), whose expression is restricted to extraembryonic tissues, is a chromosomally imprinted regulator of placental morphogenesis and trophoblast differentiation. Heterozygous female mice that inherited a mutant Esx1 allele from their father developed normally. Heterozygous females that inherited the Esx1 mutation from their mother, however, were born 20% smaller than normal and are identical in phenotype to hemizygous mutant males and homozygous mutant females. Although Esx1 mutant embryos were initially comparable in size with controls at 13.5 days post coitum (dpc), their placentas were significantly larger. Defects in the morphogenesis of the labyrinthine layer were observed as early as 11.5 dpc. Subsequently, vascularization abnormalities developed at the maternal-fetal interface, causing fetal growth retardation. These results identify Esx1 as the first essential X-chromosome-imprinted regulator of placental development that influences fetal growth, and may aid our understanding human placental insufficiency syndromes.

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Figure 1: Generation of Esx1 mutant mice.
Figure 2: Abnormal placental development and growth retardation in Esx1-deficient mice.
Figure 3: Abnormal labyrinthine layer of Esx1-deficient placenta.
Figure 4: Expression of Esx1 in XX, XEsx1X, XXEsx1, XY and XEsx1Y placental tissue.

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Acknowledgements

We thank A. Bradley for the AB-1 ES and SNL 76/7 STO cell lines, A. Nagy for the ploxPneo-1 plasmid, K. Mahon for probes, K. Dunner Jr and C. Bucana for TEM, and S. Glasser, R. Farnsworth and K. Mahon for helpful discussions. The M.D. Anderson Cancer Center High Resolution Electron Microscopy Facility is supported by an institutional core grant from the National Institutes of Health (NIH). This study was supported by NIH grant HD30284 to R.R.B.

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

    Yuanhao Li & Richard R. Behringer

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  1. Yuanhao Li
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Correspondence to Richard R. Behringer.

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Li, Y., Behringer, R. Esx1 is an X-chromosome-imprinted regulator of placental development and fetal growth. Nat Genet 20, 309–311 (1998). https://doi.org/10.1038/3129

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