The secret behind how the human heart and other organs automatically "right size" themselves has been discovered by researchers at Johns Hopkins. This secret is a protein discovered in fruit fly eyes.
The protein, named Kibra, is linked to a relay of chemical signals responsible for shaping and sizing tissue growth by coordinating control of cell proliferation and death.
The discovery could hold clues to controlling cancer.
In a series of experiments, the scientists manipulated Kibra's role in a signalling network called the Hippo pathway, which consists of several proteins working together as a braking system.
Counterparts of the components in the Hippo pathway in flies are found in most animals, suggesting that this pathway may act as a "global regulator" of organ size control, said Dr. Duojia Pan.
"People have always been curious about what makes a hippopotamus grow so much bigger than a mouse. As well as how our two hands, which develop independently, get to very similar sizes. Our studies show that Kibra regulates Hippo, which keeps organs characteristically sized, preventing my heart or your liver from becoming as hefty as those befitting a large African amphibious mammal," said Pan.
The researchers identified the gene they named Hippo in 2003, showing that an abnormal copy of it led to an unusually large eye in a developing fruit fly.
Pan said that the new experiments moved the investigation "slowly and methodically upstream" to find Hippo's trigger, where "the key to size-control lies."
Pan added that the Hippo-Kibra link could be a key to understanding and treating cancer because cancer is literally a disease of uncontrolled growth.
The Johns Hopkins and Florida State teams discovered Kibra by studying ovarian cells from adult flies and by using a gene-controlling technique called RNA interference (RNAi) to systematically turn off each of the approximately 14,000 genes in the fly genome, one at a time, in cultured fly cells.
They then analysed the function of Kibra in the developing fly larvae.
They found that the Hippo pathway was not active in the absence Kibra.
Further studies on human cells measured the activity of the Hippo pathway while manipulating human Kibra and showed that like its fruit fly counterpart, human Kibra acts as a tumour suppressor protein that regulates Hippo signalling.
"The discovery of Kibra moves us an important step closer to identifying the initial signal that triggers Hippo's activation. We're making progress along the Hippo pathway, heading toward the cell surface, and believe we will find that elusive signal en route," said Pan.
The study has been published in Developmental Cell.