During development, cells differentiate into well defined patterns through an orchestrated program in space and time. This differentiation into different cell states is coordinated by intercellular signaling and is interpreted via intracellular genetic circuits. However, many developmental processes also involve changes in cell morphology that occur concurrently with the differentiation process. How such morphological changes affect intercellular signaling? How cell morphology changes are controlled by intercellular signaling? And how the dynamic interplay between intercellular signaling, intracellular genetic circuits and regulation of cellular morphology generate the observed differentiation patterns? We will address these questions in the context of the Notch signaling pathway and Notch dependent pattern formation processes. Using a combination of micropatterning devices and quantitative time lapse microscopy, we will first measure the dependence of Notch signaling on the properties of the boundary between pairs of cells (e.g. length of boundary, molecular and mechanical properties). We will then use the information obtained from these measurements to construct mathematical models of Notch dependent pattern formation processes combining cell-cell signaling, intracellular circuitry and cell morphology in a unified manner. Such a combined experimental and theoretical approach will not only provide new insights into the Notch signaling pathway but will also provide a new framework for a whole class of developmental patterning processes involving morphological changes during differentiation.
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