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The Hippo signaling pathway has been shown to be involved in regulating cellular identity, cell/tissue size maintenance and mechanotransduction. The Hippo pathway consists of a kinase cascade which determines the nucleo-cytoplasmic localization of YAP in the cell. YAP is the effector protein in the Hippo pathway, which acts as a transcriptional cofactor for TEAD. Phosphorylation of YAP upon activation of the Hippo pathway prevents it from entering the nucleus and abrogates its function in the transcription of the target genes. In Cnidaria, the information on the regulatory roles of the Hippo pathway is virtually lacking. Here, we report the existence of a complete set of Hippo pathway core components in Hydra for the first time. By studying their phylogeny and domain organization, we report evolutionary conservation of the components of the Hippo pathway. Protein modelling suggested the conservation of YAP-TEAD interaction in  Hydra . Further, we characterized the expression pattern of the homologs of  yap, hippo, mob  and  sav  in  Hydra  using whole-mount RNA  in situ  hybridization and report their possible role in stem cell maintenance. Immunofluorescence assay revealed that  Hvul _YAP expressing cells occur in clusters in the body column and are excluded in the terminally differentiated regions. Actively proliferating cells marked by Ki67 exhibit YAP colocalization in their nuclei. Strikingly, a subset of these colocalized cells is actively recruited to the newly developing bud. Disruption of the YAP-TEAD interaction increased the budding rate indicating a critical role of YAP in regulating cell proliferation in  Hydra.  Collectively, we posit that the Hippo pathway is an essential signaling system in  Hydra ; its components are ubiquitously expressed in the  Hydra  body column and play a crucial role in  Hydra  tissue homeostasis.

Identification of Components of the Hippo Pathway in Hydra and Potential Role of YAP in Cell Division and Differentiation