Wednesday, February 5, 2025
2/5/2025
Project Summary The long-term goal of our research program is to understand and identify the mechanisms of cell shape dynamics that facilitate the emergence of tissue-wide patterns from local cell-cell communication events. The incorrect spatial and temporal induction of genes and cell behaviors by perturbed signaling can lead to catastrophic errors in development. Therefore, it is critical to understand how signaling mechanisms that take place at the level of a cell or adjacent cells are coordinated across larger tissue length scales to achieve robust patterns and support tissue homeostasis. Cytonemes, or signaling filopodia, are long actin-rich cellular protrusions that allow cells to physically interact with, and signal to, other cells at a distance. Cellular protrusions like cytonemes have been shown to play a role in many developmental processes, including spot and stripe patterning, limb patterning, stem cell niche maintenance, and neural plate patterning. Despite this, relatively little is known about the general mechanisms that regulate cytoneme-specific formation and behavior. We are interested in understanding how these protrusions are regulated both at the level of cytoskeletal mechanisms, and as an integrated part of the cell-wide and tissue-wide signaling states. To address this problem, we use the spot pattern of bristles on the dorsal thorax of the fruit fly Drosophila melanogaster as a model system. During bristle patterning, cytonemes extend from the basal surface of thoracic epithelial cells to facilitate long-range, Notch-mediated, lateral inhibition. Leveraging our strengths in Drosophila model systems genetics and quantitative live microscopy, over the next five years our goals include understanding how the formation of cytonemes are regulated, especially downstream of Notch-mediated lateral inhibition signaling. In parallel, we aim to understand how cytoneme activity contributes to cell and tissue heterogeneities that facilitate the timely formation of well-organized patterns. These studies will not only yield valuable cell biological knowledge about the specific regulation of cytonemes, but will also elucidate fundamental mechanisms that coordinate patterning across length scales.
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