Our discovery of cytonemes, specialized filopodia that orient toward cells that express signaling proteins, has led us to propose a novel mechanism that moves signaling proteins between producing and target cells. This model postulates that signaling proteins move between cells in a manner similar to the way neurotransmitters move at neuronal synapses - by transferring from pre- to post-synaptic cell at synapses. Work from my lab now shows that these non-neuronal synapses exist, that they involve proteins that have previously been shown to function and to be required at neuronal synapses, and are essential for paracrine signaling between non- neuronal cells. This direct and convincing experimental evidence firmly establishes that cytonemes ferry signaling proteins between producing and receiving cells. It also identified several unexpected properties of cytonemes that have significant implications for mechanisms of signal transduction. The work proposed in this application will develop new tools for imaging cytonemes and will build upon our previous findings to determine the roles, composition and functions of these remarkable organelles.
When cells in a developing animal grow to form tissues and organs, they often do so in response to gradients of chemical signals, yet the mechanisms by which these molecular messages move and are received is not known. Our work has provided strong evidence that thin, finger-like protrusions from cells - we call these extensions cytonemes - play a key role in this process. Research proposed in this application explores the structure and function of cytonemes and will have important implications for cell-cell signaling in all animals and in many contexts.
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