The study challenges a long-standing idea about the role of Hippo signaling in organ growth

The study challenges a long-standing idea about the role of Hippo signaling in organ growth

The Hippo signaling pathway — a genetic program thought to play a central role in organ development — fails to direct normal organ growth in flies and mice, according to a new study.

The findings, which challenge a long-standing idea about the role of Hippo signaling, suggest the need to reevaluate the pathway's function in other biological contexts, including cancer and organ regeneration. The Hippo signaling pathway is generally considered a master regulator of normal organ growth. Studies in flies and mice have shown that mutations in parts of the Hippo signaling pathway can lead to organ overgrowth.

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Based on these observations, the researchers propose that loss-of-function mutations in the core kinases or overexpression of the transcriptional coactivators Yap/Taz/Yki upregulates the expression of genes that induce cell proliferation, cell survival and tissue growth. Yap/Taz/Yki are thought to be active during the growth phase of an organ and drive cell proliferation, but are inactivated when the organ reaches maturity. However, not all findings fit this standard model.

Weronika Kowalczyk and colleagues reassessed the function of Hippo signaling during organ growth in Drosophila imaginal disc cell-derived structures such as wings and eyes, as well as in the mouse liver. Contrary to the current model, Kowalczyk et al. found that removing Hippo signaling did not affect the ability of the organs examined to grow to their normal size. Furthermore, the authors found that Yap/Taz/Yki transcriptional activity did not correlate with cell proliferation or normal organ development. Although Kowalczyk et al. discovered that the Hippo pathway does not instruct normal organ growth, the authors identified several Hippo pathway genes that were required for the excessive growth, suggesting that Hippo signaling plays a role in activating abnormal genetic programs that lead to ectopic organ development.

Source:

American Association for the Advancement of Science (AAAS)

Reference:

Kowalczyk, W., et al. (2022) Hippo signaling instructs ectopic but not normal organ growth. Science. doi.org/10.1126/science.abg3679.

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