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

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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.