An ancient role for the Hippo pathway in axis formation and morphogenesis

How did cells of early metazoan organisms first organize themselves to form a body axis? The canonical Wnt pathway has been shown to be sufficient for induction of axis in Cnidaria, a sister group to Bilateria, and is important in bilaterian axis formation. Here, we provide experimental evidence that in cnidarian Hydra the Hippo pathway regulates the formation of a new axis during budding upstream of the Wnt pathway. The target of Hippo pathway, the transcriptional co-activator YAP, inhibits the initiation of budding in Hydra , and is regulated by Hydra LATS. In addition, we show functions of Hippo pathway in regulation of actin organization and cell proliferation in Hydra . We hypothesize that Hippo pathway served as a link between continuous cell division, cell density and axis formation early in metazoan evolution. ### Competing Interest Statement The authors have declared no competing interest.