Control of cell fate decisions by dynamic signalling filopodia

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In order for a fertilised egg to develop into a multicellular organism, cells communicate with each other by sending signals that cause receiving cells to change the type of cell they become, i.e. their fate. While it was originally thought that such signals diffuse in the extracellular space until they reach the receiving cell, recently it has been shown that instead a receiving cell can extend a finger like projection, or filopodium, to directly collect the signal from the source cell. Therefore, these type of 'signalling filopodia' are a new way of thinking about cellular communication. Our research studies signalling filopodia using the classic model, the fruitfly Drosophila, as it develops quickly and is very amenable to genetics and genome engineering. Moreover, the same signals that are used during human development and tissue homeostasis are found in the fruitfly where they are also essential for development. Bone Morphogenetic Proteins (BMPs) are one of the major types of cell signals, which are necessary for development of nearly all organs and tissues. We study Drosophila germline stem cells (GSCs), which are critical for continued egg production and represent a powerful model for studying stem cells. BMPs released by other cells in the ovary are critical for maintaining the stem cell fate. Our recent data show that these GSCs make signalling filopodia to collect the BMP signal.When the GSC divides, one daughter stays as a GSC whereas the other differentiates into a different cell type. We have also detected signalling filopodia on the differentiating cells in the ovary, but their function is completely unknown. Our exciting hypothesis is that the filopodia exist on differentiating cells so that they can, when required, collect the BMP signal which induces them to revert back to a stem cell, called dedifferentiation. While dedifferentiation is critically important in the body, for example during tissue repair following injury, it is difficult to study. Here we will exploit the Drosophila model, as an experimental strategy for inducing dedifferentiation back to GSCs has been described.In this proposal we aim to determine how the signalling filopodia allow receipt of the BMP signal and in turn how this influences GSC behaviour. To achieve this goal we will use state-of-the-art microscopy approaches, which will allow us to image the signalling filopodia and the localization of proteins on them for hours at a time, to answer three key questions. Firstly, how do the signalling filopodia reach their target cells to collect the signal? Secondly, how do the filopodia control the amount of signalling inside the cell? Thirdly, do the signalling filopodia on differentiating cells collect the BMP signal to promote dedifferentiation when required?Overall our data will provide important new information in relation to this new concept for cell signalling, via signalling filopodia. Our findings will be broadly relevant to other stem cell systems, as it has been shown that different types of stem cells also use signalling filopodia to collect signals. Moreover, by identifying a role for signalling filopodia in mediating dedifferentiation back to a stem cell fate, our data will ultimately be useful in the development of improved strategies for the regeneration of damaged tissues and organs.