Hippo signaling does not direct normal organ growth

According to a new study, the Hippo signaling pathway — a genetic program thought to play a central role in organ development — does not direct normal organ growth
in fruit flies and mice.
These findings challenge long-held wisdom about the role of the Hippo signaling pathway, suggesting the need to re-evaluate the pathway's function in other biological contexts, including cancer and organ regeneration
.
The HIPPO signaling pathway is widely recognized as a major regulator of normal organ growth
.
Studies in fruit flies and mice have shown that partial mutations in the Hippo pathway can lead to organ overgrowth
.
Based on these observations, the researchers believe that loss-of-function mutations in core kinases or overexpression of the transcriptional coactivator Yap/Taz/Yki upregulate the expression
of genes that induce cell proliferation, cell survival, and tissue growth.
It is thought that Yap/Taz/Yki is active during the organ growth phase and promotes cell proliferation, but is inactive
when the organ is fully growing.
However, not all of the results of the study fit this standard model
.
Weronika Kowalczyk and colleagues re-evaluated the function of Hippo signaling during cell-derived organ growth in fruit fly organoid dishes, such as wings and eyes, as well as mouse livers
.
In contrast to the current model, Kowalczyk et al.
found that removing the hippo signal did not impair the ability
of the studied organ to grow to normal size.
In addition, the authors found that the transcriptional activity of Yap/Taz/Yki was not
associated with cell proliferation or normal organ development.
Although Kowalczyk et al.
found that the hippo pathway does not direct normal organ growth, the authors did find that several hippo pathway genes are required for overgrowth, suggesting that hippo signaling plays a role
in activating abnormal genetic programs that lead to ectopic organ development.

Hippo signaling instructs ectopic but not normal organ growth