Current Research Directions

Background​

Development and tissue homeostasis rely on the precise spatial and temporal coordination of cell fates and behaviors to generate and maintain organized tissues. This coordination is orchestrated by secreted signaling proteins, such as Fibroblast Growth Factors (FGFs), that travel from signal-producing cells to target cells through the extracellular space and activate intracellular signaling pathways. Although the intracellular pathways activated by these evolutionarily conserved signals are well characterized, a fundamental question remains: how are secreted signals distributed between cells with sufficient spatial and temporal precision to ensure that the right cells receive the right signals at the right levels and times? This precision is especially important because the same signaling pathways are iteratively deployed by cells in different developmental contexts, where differences in level, timing, location, and directionality of signal dispersion can encode distinct cellular responses, fate selections, and tissue patterns. However, the mechanisms that regulate how signals are released, transported, and delivered between cells with such precision remain incompletely understood.

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Central Premise​

​Our research builds on the discovery of signaling filopodia, known as cytonemes, and investigates how these specialized filopodia mediate selective, directed communication between signal-producing and signal-receiving cells. In contrast to traditional models in which signals are readily released and disperse passively, nonselectively through extracellular space, cytonemes can deliver signals to specific target cells through the cytoneme-cell contact sites. Signal exchange at these contact sites is conceptually analogous to communication at neuronal synapses, providing a means to regulate signal levels, duration, and timing across distance with high spatial and temporal precision and target specificity. Cytonemes and cytoneme-like signaling nanotubes have been observed in diverse developmental and physiological contexts, including stem-cell niches, and have also been implicated in disease. These findings suggest that filopodia-mediated signaling may represent a broadly conserved principle of intercellular communication. Yet the cellular and molecular mechanisms that regulate these signaling organelles remain largely unexplored. We address this gap using Drosophila tracheal and muscle progenitor niches as model systems, focusing on the cellular and molecular mechanisms that govern cytoneme-mediated FGF signaling and tissue patterning.

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Research Approach and Directions​

We combine powerful Drosophila genetics and genome editing with cell biology, biochemistry, and advanced high-resolution microscopy to visualize signal distribution and pathway activation in developing tissues and dissect how dynamic cytoneme-mediated communication shapes cell behavior, cell fate, and tissue organization. Our research addresses questions such as:

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• How do cytonemes shape and maintain complex tissue patterns?

• How are cytonemes formed, polarized, and directed toward appropriate target cells?

• How do cytonemes recognize their targets and establish selective signaling contacts?

• How are signaling proteins prepared and controlled for release only at the cytoneme contact sites?

• How are cytoneme contacts formed, maintained, and disassembled to regulate signaling dynamics?

• What happens to cells and tissues when cytoneme-mediated signaling is disrupted?​

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Given the conservation of the signaling pathways and the importance of asymmetric signaling across organisms, this research has broad implications for developmental biology and disease research and is expected to provide a conceptual framework for future advances in tissue engineering.