Role of HGF in Development of CNS Architecture

肝细胞生长因子/分散因子（HGF/SF）作为多种培养细胞的有丝分裂原、运动原和形态原发挥作用。HGF/SF及其受体（c-met原癌基因产物）的基因在胚胎期和成年期的许多组织中表达。认为HGF/SF在小鼠发育期间介导间充质和上皮之间的信号交换。具有HGF/SF基因的靶向破坏的小鼠胚胎具有严重受损的胎盘，胎盘滋养层细胞的数量显著减少，并且在出生前死亡。HGF/SF在体外可刺激滋养层细胞的生长，在正常胚胎原代培养中，尿囊液可释放HGF/SF活性，而突变胚胎则无此活性。这些观察结果表明，HGF/SF是胎盘器官发生所需的尿囊间充质-滋养层上皮相互作用的重要介质。为了进一步研究HGF在中枢神经系统（CNS）结构发育后期的作用，通过四倍体聚集方法挽救了突变胚胎的胎盘缺陷。使用这些拯救的突变体，CNS的组织学分析正在研究中。

Hepatocyte growth factor/scatter factor (HGF/SF) functions as a mitogen, motogen and morphogen for a variety of cultured cells. The genes for HGF/SF and its receptor (the c-met proto-oncogene product) are expressed in many tissues during the embryonic periods and in the adult. HGF/SF is thought to mediate a signal exchange between the mesenchyme and epithelia during mouse development. The mice embryos with a targeted disruption of the HGF/SF gene 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 observations show that HGF/SF is an essential mediator of allantoic mesenchyme-trophoblastic epithelia interaction required for placental organogenesis. To investigate further role for HGF in later stage of development of central nervous system (CNS) architecture, the placental defect of the mutant embryos was rescued by tetraploid aggregation methodology. Using these rescued mutants, histological analysis of CNS are under investigation.