An ancient role for the Hippo pathway in axis formation and morphogenesis

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

A PAK family kinase and the Hippo/Yorkie pathway modulate WNT signaling to functionally integrate body axes during regeneration

“…In other organisms, these pathways are known to function upstream of YKI/YAP, which is critical for cell number and organ size ( 80 – 83 ). However, in animals with indeterminate growth like planaria and Hydra , YKI/YAP patterns the body axes by modulating WNT signaling ( 37 , 38 , 84 , 85 ). In Hydra , WNT signaling indirectly regulates body size by patterning the oral-aboral axis ( 86 ).…”

A PAK kinase family member and the Hippo/Yorkie pathway modulate WNT signaling to functionally integrate body axes during regeneration

“…In other organisms these pathways are known to function upstream of YKI/YAP, which is critical for cell number and organ size (Codelia et al, 2014; Csibi and Blenis, 2012; Ibar and Irvine, 2020; Sayedyahossein et al, 2020). However, in animals with indeterminate growth like planaria and Hydra , YKI/YAP patterns the body axes by modulating WNT signaling (Brooun et al, 2022; Lin and Pearson, 2014, 2017; Unni et al, 2021). In Hydra , WNT signaling indirectly regulates body size by patterning the oral-aboral axis (Mortzfeld et al, 2019).…”