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The LIM homeobox gene Lhx9 is essential for mouse gonad formation

Nature volume 403, pages 909–913 (2000)Cite this article

Abstract

During mammalian embryonic development, the ovaries and testes develop from somatic cells of the urogenital ridges as indifferent gonads, harbouring primordial germ cells that have migrated there. After sex determination of the gonads, the testes produce testosterone and anti-Mullerian hormone which mediate male sexual differentiation, and the female developmental pathway ensues in their absence1,2,3. Here we show that transcripts of the LIM homeobox gene Lhx9 are present in urogenital ridges of mice at embryonic day 9.5; later they localize to the interstitial region as morphological differentiation occurs. In mice lacking Lhx9 function, germ cells migrate normally, but somatic cells of the genital ridge fail to proliferate and a discrete gonad fails to form. In the absence of testosterone and anti-Mullerian hormone, genetically male mice are phenotypically female. The expression of steroidogenic factor 1 (Sf1), a nuclear receptor essential for gonadogenesis2, is reduced to minimal levels in the Lhx9-deficient genital ridge, indicating that Lhx9 may lie upstream of Sf1 in a developmental cascade. Unlike mice lacking other genes that mediate early stages of gonadogenesis4,5,6, Lhx9 mutants do not exhibit additional major developmental defects. Thus, LHX9 mutations may underlie certain forms of isolated gonadal agenesis in humans.

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Figure 1: Lhx9 expression in the developing murine gonad.
Figure 2: Reproductive tract of 3-month-old Lhx9+/+ female (a, c, e, g) and sibling Lhx9-/– mutant male (b, d, f, h).
Figure 3: Arrest of gonad formation in Lhx9 mutants.
Figure 4: Analysis of the defects in gonad formation in Lhx9 mutant embryos (b, d, f, h, j, n) as compared with wild-type controls (a, c, e, g, i, m).

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Acknowledgements

We thank R. Lovell-Badge for Dax1, Amh and Sox9 probes; J.B.L. Bard, K. Pfeifer and A. Tomac for comments on the manuscript; L. Nieman for fruitful discussions; and J. Levine for assistance. L.Z. and K.L.P. are supported by the NIH.

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Authors and Affiliations

  1. Laboratory of Mammalian Genes and Development and ,

    Ohad S. Birk, Delane E. Casiano, Yangu Zhao, Alexander Grinberg, SingPing Huang & Heiner Westphal

  2. Heritable Disorders Branch, National Institute of Child Health and Human Development, NIH, Bethesda, 20892, Maryland , USA

    Christopher A. Wassif & Forbes D. Porter

  3. Genetics Department, Medicine Branch National Cancer Institute, NIH, Bethesda, 20889, Maryland, USA

    Tiziana Cogliati

  4. Department of Internal Medicine University of Texas Southwestern Medical Center, Dallas, 75235, Texas, USA

    Liping Zhao & Keith L. Parker

  5. Department of Medicine Children's Hospital, Boston, 02115, Massachusetts, USA

    Jordan A. Kreidberg

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  1. Ohad S. Birk
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Correspondence to Heiner Westphal.

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Birk, O., Casiano, D., Wassif, C. et al. The LIM homeobox gene Lhx9 is essential for mouse gonad formation . Nature 403, 909–913 (2000). https://doi.org/10.1038/35002622

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