The Hippo pathway regulates axis formation and morphogenesis in <i>Hydra</i>.

Abstract

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 <i>Hydra</i> the Hippo pathway regulates the formation of a new axis during budding upstream of the Wnt pathway. The transcriptional target of the Hippo pathway, the transcriptional coactivator YAP, inhibits the initiation of budding in <i>Hydra</i> and is regulated by <i>Hydra</i> LATS. In addition, we show functions of the Hippo pathway in regulation of actin organization and cell proliferation in <i>Hydra</i>. We hypothesize that the Hippo pathway served as a link between continuous cell division, cell density, and axis formation early in metazoan evolution.