THE BIOLOGY OF RON/STK, A RECEPTOR TRYOSINE KINASE.

该项目的长期目标是通过小鼠模型了解Ron（酪氨酸激酶受体）在植入和早期发育过程中的生物学功能。初步研究将集中在野生型动物胚胎着床过程中Ron及其配体肝细胞生长因子样蛋白的时空特征。接下来，将通过表征Ron -/-胚胎周围滋养细胞的分化和侵袭能力，确定着床过程中与Ron功能缺失相关的异常表型，并探讨删除该受体的影响。最后，通过在已建立的滋养细胞系（从野生型到高度侵袭型）中失活或过表达Ron受体来操纵Ron受体，以阐明植入过程中配体诱导Ron激活的分子机制。这些实验不仅有助于更好地了解Ron在哺乳动物着床和早期发育过程中的表达和功能，还可能提示子宫腺瘤和异位妊娠等侵袭性疾病中Ron功能异常的潜在意义。

The long term goal of this project is to understand the biological function(s) of Ron, a receptor tyrosine kinase during implantation and early development using a murine model. Initial studies will focus on the temporal and spatial characterization of Ron and its ligand, hepatocyte growth factor-like protein, during embryonic implantation in wild type animals. Next, the abnormal phenotype correlated with the loss of Ron function during implantation will be determined and the effect of deleting this receptor will be explored by characterizing the differentiation and invasion ability of trophoblast cells surrounding Ron -/- embryos. Finally, manipulation of the Ron receptor via inactivation or overexpression in established trophoblast cell lines (ranging from wild type to highly invasive) will be performed to elucidate the molecular mechanisms involved in ligand induced Ron activation during implantation. These experiments will not only lead to a better understanding of Ron expression and function during mammalian implantation and early development but may also implicate the potential significance of Ron function anomalies during invasive conditions such as uterine adenomas and ectopic pregnancies.