The atypical cadherin Fat (Ft) is crucial for planar cell polarity (PCP) in Drosophila. Four ft homologs (Fat1 to Fat4) have been identified in mammals, but the functional roles of these homologs and any possible redundancies between them are unclear. Here, Helen McNeill and colleagues study the genetic interactions between mammalian Fat genes and show that Fat proteins act both synergistically and antagonistically to regulate multiple aspects of tissue morphogenesis in mice (). For example, the authors show that Fat1 and Fat4 synergise during kidney, cochlea and cranial neural tube morphogenesis. Importantly, the researchers also show that the effects of Fat4 are modulated by atrophins, which are known components of PCP signalling in Drosophila, suggesting that Fat-atrophin interactions play an essential and conserved role in planar polarity. These findings reveal a high degree of complexity in mammalian PCP and highlight the wide-ranging effects of Fat cadherins on animal development.
