Molecular genetics of cell niche and radiation sensitivity in tissue construction of Oryzias latipes

为了建立组织干细胞DNA损伤反应的研究体系，本研究在青鳉中建立了两条不同途径的突变体。一个是信号转导通路，负责DNA损伤。ATM、ATR和DNA-PKcs是PI 3激酶家族的成员。这些基因产物在损伤反应的起始阶段起重要作用。我们已经建立了ATM和ATR突变体。在本研究中，我们确定了DNA-PKcs突变体。我们还获得了p53突变体，其在损伤反应中也起重要作用。我们的目标是使用这些携带单个或多个突变的突变体来分析青鳉的损伤反应。另一个是调节组织中细胞生长的信号通路。Wnt信号通路是一组信号转导通路，其导致转录和细胞生长的调节。这些信号传导途径通过Wnt配体与卷曲家族受体的结合而被激活。为了建立调控细胞生长的系统，我们建立了卷曲突变体。这些突变体的建立使我们能够研究损伤反应和生长信号之间的串扰。

To develop the system to study DNA damage response in tissue stem cell, in this study we have established several mutants in two different pathways in Medaka. One is the signal transduction pathway, responsibility to DNA damage. ATM, ATR and DNA-PKcs are member of PI3 kinase family. These gene products play an important role on the initial step of damage response. We have already established ATM and ATR mutants. In this study we have identified DNA-PKcs mutant. We have also obtained p53 mutant, which also play essential role on damage response. Our goal is to analyze the damage response in Medaka using these mutants carrying a single or a multiple mutation. Another is the signaling pathway which regulates cell growth in tissue. The Wnt signaling pathways are a group of signal transduction pathways, which leads to regulation of transcription and cell growth. These signaling pathways are activated by the binding of a Wnt ligand to a Frizzled family receptor. To establish system to regulate cell growth, we haveestablished Frizzled mutants. Establishment of these mutants enables us to study the cross-talk between damage response and growth signaling.