Cell Polarization in Response to Wnt Signaling in C. elegans

细胞通常以蛋白质的形式相互传递信息，这些蛋白质从一个细胞分泌出来，并在邻近细胞的表面接收。一个重要的信号蛋白家族被称为“Wnt”家族。Wnt家族蛋白对胚胎细胞和成体干细胞的极化至关重要，即将特定的细胞成分定位在细胞的一侧。Wnt信号在癌症中也起着关键作用，细胞极性的丧失是许多癌症的早期标志。因此，人们对了解Wnt信号如何使细胞极化产生了极大的兴趣。Wnt信号是作为细胞极化的位置信号，还是作为允许信号与未知的位置信号一起起作用，长期以来一直是一个争论的问题。该项目使用了一种创新的系统，在该系统中，人们可以将Wnt信号源定位在单个细胞上，并通过显微镜拍摄荧光标记蛋白的运动来跟踪活细胞中的细胞极化。使用该系统的初步结果产生了一个惊喜：尽管表达Wnt的细胞可以作为细胞极化的位置线索，但纯化的活性Wnt蛋白却不能。这一结果提出了一种可能性，即Wnt蛋白可能是由未知信号引导的细胞极化的许可信号。这一假设将被检验以揭示细胞极化的确切机制，并通过识别参与这些机制的重要分子。这个项目也将训练学生进行研究。

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.