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 Our laboratory aims to understand a fundamental question in Cell and Developmental Biology: how do cells in multicellular organisms communicate with morphogenetic signals to coordinate and organize themselves into complex patterns in developing organs. Cells employ myriad of conserved signaling proteins such as Bone morphogenetic proteins (BMPs), Fibroblast growth factors (FGFs), Hedgehog, and WNT to communicate. Understanding how cells exchange these signals is the key to understanding how cells cooperate to form organized tissues during development, and why cells in various diseases lose or escape their normal controls.   

We investigate a unique mechanism of cell-cell communication

There is a lacuna in understanding how the

morphogenetic signals disperse from one cell to another, and how cells, in a rapidly developing

tissue, spatiotemporally control signal delivery. We explore a recently discovered mechanism that may ensure cells to actively control signal dispersion. In this process cells extend many specialized membrane projections or filopodia, named cytonemes to reach out and exchange signals by directly touching one another. Our lab aims to unfold the processes in signal 

sending and recipient cells that mediate this contact-dependent signalingand to investigate how cells may employ this mode of signaling to create complex patterns.

Contact-mediated signaling in Drosophila tracheal morphogenesis

To unravel the mysteries of the cell-cell signaling we take advantage of the well established genetic model organism, Drosophila, and we focus on one of the essential metazoan signaling proteins, FGF. We investigate FGF signaling during the morphogenesis of the trachea. Tracheal tissues constitute a complex branched tubular network to transport O2 and CO2. The Drosophila FGF, Branchless, acts as a positional cue for the migration and organization of the tracheal cells into the branched tubular network. During this branching morphogenesis migrating tracheal cells extend polarized cytonemes to contact the FGF producing cells. When the cytonemes are impaired to contact the signal source, recipient tracheal cells fail to activate signaling and eventually stop migrating toward the source. Our preliminary observations suggest that tracheal cytonemes are necessary to receive FGF. Many of these attributes of FGF signaling in trachea are ideal to uncover the mechanism of the cytoneme-mediated communication. 

ASP cytonemes contact FGF source
ASP cytonemes contact FGF source
Embryo trachea, FGFR:Cherry
Embryo cytonemes,
FGFR:Cherry

Currently, we investigate i) how tracheal cytonemes find FGF source, exchange and transport signals, ii) how FGF is controlled for release and uptake, and iii) how cytoneme-mediated FGF signaling may organize tracheal cells into the branched tubular network. To image the cells and the signaling molecules in developing organs we employ live-cell microscopy. In addition, we use a number of genetic, genome editing, molecular-, cell- and developmental- biology techniques to manipulate and investigate the activities of the cells and signals. Revealing the mechanisms that the cells use to communicate with conserved signaling proteins such as FGF will have fundamental implications for our understanding of both normal development and diseases. 

 

 

Roy-scopes

 

 

 

 

Funding

NIH/NIGMS (MIRA-R35, Outstanding Investigator Award)

NIH/NHLBI (R00/K99, Pathway to Independence)

 

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