Coordination of planar cell polarity pathways through Spiny-legs

摘要

Animals have many asymmetric organs. Wings, for example, are aerodynamically shaped and have a clear front, back, top and bottom, and even additions to these organs, such as feathers on the wing, often need to be oriented in a specific manner. This kind of orientation arises when cells divide and grow asymmetrically in a flat plane. The asymmetry is established at the level of single cells when proteins are not equally spread throughout a cell, but rather asymmetrically distributed. Such cells are said to be ‘planar polarized’; and many experiments addressing this so-called planar cell polarity have been conducted in fruit flies, because they can be genetically altered easily. Previous studies have shown that two signaling pathways—called Frizzled and Dachsous-Fat—regulate how individual cells orient themselves within a flat sheet of cells that forms fruit fly’s wing. The two pathways are not independent, but it is unclear how they are linked. In particular, there has been conflicting evidence as to whether the Dachsous-Fat pathway controls the Frizzled pathway or whether the two act in parallel. Now, Ambegaonkar and Irvine have discovered new roles for a protein that is involved in both pathways, called 'Spiny-legs'. This protein was known to be important in the Frizzled pathway, but, when it was tracked with a fluorescent tag in developing wing cells it also accumulated in areas where two proteins that make up part of the Dachsous-Fat pathway were located. Biochemical experiments showed that both of these proteins (which are called Dachs or Dachsous) could physically interact with Spiny-legs. Ambegaonkar and Irvine therefore deleted the genes for Dachs or Dachsous in fruit flies and observed that Spiny-legs no longer organized itself in the proper way, implying that Dachs and Dachsous control where Spiny-legs goes within cells. When this analysis was extended to other fruit fly organs, such as the eyes, Ambegaonkar and Irvine found that Dachsous was more important than Dachs for the correct localization of Spiny-legs. Additionally, the Frizzled and Dachsous-Fat pathways seemed to compete for interactions with Spiny-legs. This connection between the two pathways helps to explain how cells behave when several different signals reach them. It also shows how different organs can reuse conserved components of the pathways to make different end products. Future studies should aim to work out the number of systems that polarize cells and how they are connected in different tissues.