Assembling a Hippo: the evolutionary emergence of an animal developmental signaling pathway.

Components of the Hippo kinase module are present in some unicellular organisms, and unicellular orthologs of the Hippo pathway kinase Warts have the capability to phosphorylate Yorkie, despite the absence of Yorkie in many of these organisms. A complete core Hippo pathway, including the transcriptional coactivator Yorkie, predated the origin of animals, and is present in the closest unicellular relatives of animals. Functional studies in unicellular organisms and early-branching animals suggest that an ancestral function of the Hippo pathway was regulation of the actomyosin cytoskeleton, and that the pathway was subsequently co-opted for tissue size regulation in the lineage leading to bilaterian animals. Acquisition of the ability of Yorkie to regulate cell proliferation and tissue size regulation may have coincided with the evolutionary emergence of distal enhancer-mediated gene regulation in animals. Decades of work in developmental genetics has given us a deep mechanistic understanding of the fundamental signaling pathways underlying animal development. However, little is known about how these pathways emerged and changed over evolutionary time. Here, we review our current understanding of the evolutionary emergence of the Hippo pathway, a conserved signaling pathway that regulates tissue size in animals. This pathway has deep evolutionary roots, emerging piece by piece in the unicellular ancestors of animals, with a complete core pathway predating the origin of animals. Recent functional studies in close unicellular relatives of animals and early-branching animals suggest an ancestral function of the Hippo pathway in cytoskeletal regulation, which was subsequently co-opted to regulate proliferation and animal tissue size. Decades of work in developmental genetics has given us a deep mechanistic understanding of the fundamental signaling pathways underlying animal development. However, little is known about how these pathways emerged and changed over evolutionary time. Here, we review our current understanding of the evolutionary emergence of the Hippo pathway, a conserved signaling pathway that regulates tissue size in animals. This pathway has deep evolutionary roots, emerging piece by piece in the unicellular ancestors of animals, with a complete core pathway predating the origin of animals. Recent functional studies in close unicellular relatives of animals and early-branching animals suggest an ancestral function Hippo pathway of cytoskeletal regulation, which was subsequently co-opted to regulate proliferation and animal tissue size. [ABSTRACT FROM AUTHOR]