期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：29
DOI：10.1073/pnas.2203257119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
The evolution of a body plan in multicellular organisms is a central problem in biology. Here, we provide genetic evidence of the involvement of the Hippo cascade, a key growth regulating pathway in axis formation in
Hydra, an early emerging metazoan. We demonstrate that the Hippo kinases regulate YAP upstream of Wnt signaling in axis formation and show that YAP and Hippo kinase pathway regulation of cell proliferation and control of the actin cytoskeleton were established early in metazoan evolution. Based on our results we speculate that Hippo signaling and nuclear Yap served to link continuous cell division, cell density, and axis formation early in metazoan evolution.
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 transcriptional target of the Hippo pathway, the transcriptional coactivator YAP, inhibits the initiation of budding in
Hydra and is regulated by
Hydra LATS. In addition, we show functions of the Hippo pathway in regulation of actin organization and cell proliferation in
Hydra. We hypothesize that the Hippo pathway served as a link between continuous cell division, cell density, and axis formation early in metazoan evolution.
