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Receptor Tyrosine Kinase Ron Is Expressed in Mouse Reproductive Tissues During Embryo Implantation and Is Important in Trophoblast Cell Function¹

^a Divisions of Developmental Biology ^b Hematology/Oncology, Cincinnati Children's Research Foundation, Cincinnati, Ohio 45229

Ron is a receptor tyrosine kinase that is activated by the binding of hepatocyte growth factor-like (HGFL) protein. Mutations in the catalytic domain of this receptor result in an aggressively invasive phenotype. Conversely, deletion of the entire receptor results in an embryonic lethality by Embryonic Day 7.5. The specific cellular localization and mechanisms of action of Ron and HGFL during embryo implantation are not known. Therefore, this report characterizes the temporal and spatial distribution of this receptor during mouse embryo implantation and placentation. Reverse transcription-polymerase chain reaction analysis demonstrated the presence of Ron transcripts in the uterus, placenta, testis, and epididymis, whereas HGFL transcripts were found in the cervix, placenta, epididymis, and testis. In situ hybridization and immunohistochemical analyses demonstrated that Ron was present in the cells of the ectoplacental cone and trophoblast giant cell regions surrounding the implanting embryo. Ron expression was also observed in SM9-1, SM9-2, and SM-10 murine trophoblast cell lines. To determine the effects of Ron activation on trophoblast function, Matrigel invasion and cell survival assays were performed using the SM9-1 and SM-10 trophoblast cell lines. The HGFL stimulation of these cells increased invasion and enhanced cell survival. These observations suggest that activation of the Ron receptor by HGFL binding may aid in implantation by way of trophoblast function and viability.

¹ Supported by grants F32 HD08659 (K.A.H.), HD36888 (S.E.W.), T32 HD43005 (E.L.C.), DK47003 (S.J.F.D.), and DK58182 (S.J.F.D.) from the National Institutes of Health.

² Correspondence: Sandra J.F. Degen, Division of Developmental Biology, Cincinnati Children's Research Foundation, 3333 Burnet Ave., Cincinnati, OH 45229. FAX: 513 636 4317; sandra.degen{at}cchmc.org

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