institute of stem cell research

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Planar cell polarity (PCP) is essential for asymmetric cell division, coordinate cell migration and orientation of cells within the plane of an epithelium. Recently, we identified Flattop (Fltp) as a novel gene involved in gastrula organizer formation (Tamplin et al., 2008). To analyze Fltp function, we generated a knock-in allele. Interestingly, the lacZ reporter expression shows a unique tissue distribution in mono- and multiciliated cells of the inner ear (IE) and lung. Loss-of-gene function in multiciliated lung epithelial cells leads to basal body docking defects, which result in loss of cilia. Fltp mutation in the IE results in duplication of one outer hair cell row and mild rotation of hair cells. Our observation that loss of Fltp causes PCP phenotypes in the IE and the lung, together with the fact that Fltp localizes in a PCP–like asymmetric fashion in sensory IE cells and interacts with the core PCP molecule Celsr1 indicates that we have identified a novel PCP molecule important for development of ciliated tissues.

[1] Claude A. Van Campenhout, Andrea Eitelhuber, Christian J. Gloeckner, Patrizia Giallonardo, Moritz Gegg, Heide Oller, Seth G. N. Grant, Daniel Krappmann, Marius Ueffing, and Heiko Lickert: Dlg3 trafficking and apical tight junction formation is regulated by Nedd4 and Nedd4-2 E3 ubiquitin ligases. Dev. Cell in press (2011)