Mechanisms of Cell Communication in Animal Development

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SUMMARY The broad objective of my research is to answer a major question in cell and developmental biology: how do cells communicate morphogenetic signals to create tissue patterns in animals. Within a developmental field cells can precisely regulate the levels, timing and location of signal exchange. Any aberration in this control mechanism leads to developmental malformations and disease. Most existing models propose that signaling proteins diffuse in the extracellular space to generate concentration gradients, and that these extracellular gradients regulate growth, migration and patterning of target cells. However, a major focus of my research program is to understand a radically different mechanism - the ‘direct delivery’ of signals by specialized actin- rich signaling filopodia, named cytonemes. My previous work explored and first established the functional role of this novel mechanism in Drosophila. My work showed that cells use cytonemes to directly exchange signals and that cytoneme-mediated signaling is essential for cell-cell communication. My recent work is focused on Fibroblast Growth Factor (FGF), a key signaling protein in metazoan development, and its dispersion from cell to cell by cytonemes. We demonstrated that FGF acts as a morphogen that elicits concentration-dependent responses during tracheal development, that the FGF gradient is controlled by protease-dependent cleavage of the molecule, and that the FGF gradient is formed by cytoneme-mediated signaling. Recently, we also have uncovered a complex post-translation processing of FGF that may control its contact-dependent exchange. My current research is taking advantage of powerful state-of-the art microscopic imaging, biochemistry, cell biology and Drosophila genetics to continue to explore and investigate the mechanisms that control cytoneme mediated signal exchange and signal dispersion. Given the conservation of signaling mechanisms in all animals, our research will have a lasting impact on knowledge about development and disease in humans.