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Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor

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Abstract

HEPATOCYTE growth factor/scatter factor (HGF/SF) functions as a mitogen, motogen and morphogen for a variety of cultured cells1–7. The genes for HGF/SF and its receptor (the c-met protooncogene product8) are expressed in many tissues during the embryonic periods and in the adult9–14. HGF/SF is thought to mediate a signal exchange between the mesenchyme and epithelia during mouse development15. To examine the physiological role of HGF/SF, we generated mutant mice with a targeted disruption of the HGF/SF gene. Here we report that homozygous mutant embryos have severely impaired placentas with markedly reduced numbers of labyrinthine trophoblast cells, and die before birth. The growth of trophoblast cells was stimulated by HGF/SF in vitro, and the HGF/SF activity was released by allantois in primary culture of normal but not mutant embryos. These findings suggest that HGF/SF is an essential mediator of allantoic mesenchyme-trophoblastic epithelia interaction required for placental organogenesis.

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Authors and Affiliations

  1. Institute for Liver Research, Kansai Medical University, Moriguchi, Osaka, 570, Japan

    Yoshihiko Uehara & Naomi Kitamura

  2. Department of Cell Biology, Cancer Institute, Tokyo, 170, Japan

    Yoshihiko Uehara, Osamu Minowa, Junko Kuno & Tetsuo Noda

  3. Department of Anatomy, Kyoto University, School of Medicine, Kyoto, 606, Japan

    Chisato Mori & Kohei Shiota

Authors
  1. Yoshihiko Uehara
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  2. Osamu Minowa
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  3. Chisato Mori
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  4. Kohei Shiota
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  5. Junko Kuno
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  6. Tetsuo Noda
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  7. Naomi Kitamura
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Uehara, Y., Minowa, O., Mori, C. et al. Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor. Nature 373, 702–705 (1995). https://doi.org/10.1038/373702a0

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  • DOI: https://doi.org/10.1038/373702a0

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