2017-01-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/679695摘要：During animal development, spatial and temporal signals are integrated to generate elaborate patterns of cell migration. Compared to spatial signals, temporal regulation is relatively unexplored, and the mechanisms integrating both temporal and spatial signals are largely unknown. Despite of much qualitative and descriptive information is known for cell migration, very few quantitative or predictive models have been built to describe the dynamic pattern of cell migration during development. In addition, little is known about the molecular basis that leads to temporal development variations observed in isogenic populations. In order to understand how organisms faithfully develop to generate reproducible cell migration patterns, we aim to answer the following important questions: 1.How do the phenotypes (in various migration patterns) correlate with fluctuation of the output gene? 2.Clarify the roles of averaged level and fluctuations in gene expression in determining the phenotypes. 3.How does an organism achieve robust control in the development? In order to answer these questions, we plan to study cell migration in C. elegans with the following specific aims: 1.To investigate the role of output gene (unc-5) threshold level on phenotypic heterogeneity in cell migration. 2.To test the noise in input and output gene expression on phenotypic heterogeneity. 3.To explore the robustness of F-box protein (DRE-1) regulations in cell migration. Our studies will provide the mechanism underlying phenotypic heterogeneity in the timing of cell migration and the molecular basis of the noise filtering capacity by the protein-degradation regulation using both experiments and computational modeling.<br> Abstract: During animal development, spatial and temporal signals are integrated to generate elaborate patterns of cell migration. Compared to spatial signals, temporal regulation is relatively unexplored, and the mechanisms integrating both temporal and spatial signals are largely unknown. Despite of much qualitative and descriptive information is known for cell migration, very few quantitative or predictive models have been built to describe the dynamic pattern of cell migration during development. In addition, little is known about the molecular basis that leads to temporal development variations observed in isogenic populations. In order to understand how organisms faithfully develop to generate reproducible cell migration patterns, we aim to answer the following important questions: 1.How do the phenotypes (in various migration patterns) correlate with fluctuation of the output gene? 2.Clarify the roles of averaged level and fluctuations in gene expression in determining the phenotypes. 3.How does an organism achieve robust control in the development? In order to answer these questions, we plan to study cell migration in C. elegans with the following specific aims: 1.To investigate the role of output gene (unc-5) threshold level on phenotypic heterogeneity in cell migration. 2.To test the noise in input and output gene expression on phenotypic heterogeneity. 3.To explore the robustness of F-box protein (DRE-1) regulations in cell migration. Our studies will provide the mechanism underlying phenotypic heterogeneity in the timing of cell migration and the molecular basis of the noise filtering capacity by the protein-degradation regulation using both experiments and computational modeling.線蟲異質性結合計算與實驗策略C. elegansHeterogeneitycomputational and experimental strategies