Cell Polarization in Response to Wnt Signaling in C. elegans

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Cells often send messages to each other in the form of proteins secreted from one cell and received at the surface of a neighboring cell. One important family of signaling proteins is called the "Wnt" family. Wnt family proteins are essential for embryonic cells and adult stem cells to polarize, i.e., to position specific cellular components on one side of a cell. Wnt signaling also plays critical roles in cancer, and loss of cell polarity is an early hallmark of many cancers. As a result, there is great interest in understanding exactly how Wnt signals work to polarize cells. Whether Wnt signals function as positional cues for cell polarization, or alternatively as permissive signals that function with unknown positional cues, has long been a matter of debate. This project uses an innovative system in which one can position a Wnt signaling source on a single cell and follow cell polarization in living cells by filming the movements of fluorescently-tagged proteins through a microscope. Preliminary results using this system have produced a surprise: Although Wnt-expressing cells can function as positional cues for cell polarization, purified, active Wnt protein cannot. This result raises the possibility that Wnt proteins may be permissive signals for cell polarization directed by as-yet unknown cues. This hypothesis will be examined to reveal the exact mechanisms of cell polarization, and by identifying important molecules involved in these mechanisms. This project will also train students to conduct research.