旭硝子財団助成研究成果報告2023
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yrammuS 要概is essential for the safe and proper functioning of the neural network. During cortical development, excitatory neurons generated near the ventricles migrate long distances to the pial surface and stop their migration, and later-born neurons pass through the early-born neurons that have completed their migration earlier. Therefore, precise placement of neurons in the superficial layers of the neocortex is an important step in layer formation, but the details of the placement mechanism after migration has not been clarified to date. In this study, we hypothesized that cell adhesion factors downstream of the extracellular glycoprotein Reelin, which has an important function in cortical layer formation, contribute to the termination of neuronal migration and place-ment, and found several candidate molecules. We further investigated the mechanism of action of these cell adhesion molecules by developing a culture system that recapitulates the dynamic changes in cell adhesion ability of migrating neurons.細胞内の核酸(DNAやRNA)は,細胞内環境に依存して非二重らせん構造を形成し,遺伝子発現が制御される.したがって,環境依存的な遺伝子発現を情報化し,予測する技術の開発が求められている.そこで本研究では,非二重らせん構造の一種であるi-motif型DNAの細胞内での構造安定性をDNA配列から予測し,遺伝子発現に及ぼす影響を定量的に導く手法の開発を検討した.溶液の水の活量変化,共溶質による排除体積効果,およびi-motif型DNAの立体構造変化が,i-motif型DNAの構造安定性に及ぼす影響をデータベース化することで,細胞内のような多様な分子クラウディング環境に応じて変化するi-motif型DNAの構造安定性を予測システムの開発に成功した.Nucleic acids (DNA and RNA) in cells form non-duplex structures depending on the intracellular environ-ment to regulate gene expression. Therefore, it has been required to develop a technology to predict environ-ment-dependent gene expression. In this study, we examined the development of a method to predict the structural stability and efficiency of gene expression of i-motif DNA, which is a typical non-duplex structure, from the DNA sequence in cells. By compiling a database of the effects of changes in the water activity of solution, excluded volume effects due to co-solutes, and conformational changes on the stability of i-motif DNA, we successfully developed a prediction system to obtain the i-motif stability according to diverse mo-lecular crowding environments such as those in the cells.高橋俊太郎38Shuntaro TAKAHASHI環境依存的な遺伝子発現の情報化とその予測システムの開発(2021採択)Development of the prediction system of gene expression depending on the environment(Project 2021)43Rep. Grant. Res., Asahi Glass Foundation (2023)

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