Functional characterization of salvador and warts in planarians

Abstract

In the last years, the Hippo signaling has emerged as an essential pathway to control tissue and organ homeostasis, and its deregulation leads to tumoral transformation in all animals studied. However, the underlying cellular and molecular mechanism of this transformation are still not clear. The core of the Hippo pathway includes a kinase cassette composed by the kinases Hippo, Salvador, Mats, and Warts that in turn phosphorylates the nuclear effector of the pathway, Yorkie, targeting it to proteasomal degradation. Recently, the functional study of hippo, in planarians, flatworms that continuously change their size and renew their tissues according to nutrients, allowed demonstrating that the underlying mechanism of cellular transformation was not an increase in cell proliferation but inducing cell cycle arrest and promoting cell dedifferentiation. However, the functional study of yorkie did not allow to relate it with the Hippo function. Here, we show that inhibition of salvador and warts phenocopies the defects observed in hippo RNAi planarians. Since Warts is responsible for phosphorylating yorkie, this data suggests that not only the kinase cassette of the Hippo pathway is functionally conserved but also the nuclear effector.