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In development. Researchers are revealing the hormonal pathways that determine why animals stop growing before they reach horror movie dimensions.

In development. Researchers are revealing the hormonal pathways that determine why animals stop growing before they reach horror movie dimensions.


Why Spiders Don't Grow to Horrific Size

It’s no secret that a mouse stops growing before it becomes the size of a whale. But the physiological and genetic mechanisms that control how fast—and how big—an animal grows have largely remained a mystery. A study of fruit flies, however, is shedding some new light on how animals regulate body size, and may also help explain why certain cancer tumors grow out of control.

Two largely independent processes determine how big an animal gets. The first controls how fast an animal grows and depends on insulin or similar hormones to cue cells to grow and divide. The second regulates the timing of maturation or, in insects, metamorphosis (the process by which a caterpillar turns into a butterfly). In fruit flies, for instance, two hormones influence the timing of metamorphosis. One is ecdysone, known as the molting hormone because elevated levels can prompt an insect to shed an old skin or undergo other changes. The other is juvenile hormone (JH), which stops growth and initiates metamorphosis when levels drop.

Past studies have shown that researchers can influence insect size by tinkering with these hormonal pathways. In a 2010 study, for instance, scientists created fruit flies unable to produce growth-stopping JH. The result: stunted adults that were only 75% of the usual size, many of which died before reaching adulthood. But it wasn’t clear why. One possibility was that the loss of JH shortened a key growth phase and triggered premature metamorphosis, causing smaller larvae to transform into smaller adults. Alternatively, the loss of JH might have simply slowed the rate of growth but not changed the timing of metamorphosis.

To sort it out, a team led by developmental biologist Christen Mirth of the Instituto Gulbenkian de Ciência in Oeiras, Portugal, and fly geneticist Alexander Shingleton of Lake Forest Collegein Illinois bred both normal and JH-deficient flies, and then compared a suite of characteristics, including the timing of growth and levels of growth hormones. JH-deficient flies did not metamorphose prematurely, suggesting that the second hypothesis was correct, the team reports online this week in the Proceedings of the National Academy of Sciences. Surprisingly, however, the researchers also found that they could eliminate the stunting effect by altering a JH-deficient fly’s ability to produce the other two growth-related hormones. A JH-deficient fly would grow to normal size, for example, if they used genetic techniques to boost ecdysone levels or prevent it from turning off insulin production.

This extensive crosstalk between the hormones was surprising, Mirth says. It appears that “JH acts to fine-tune growth rates” by influencing the effects of the other two hormones, she says.

If the findings hold true in other kinds of insects and animals, they could help reveal universal mechanisms of growth and size regulation, says Yuichiro Suzuki, an assistant biology professor at Wellesley College in Massachusetts, who was not involved in the work.

The hormonal crosstalk may also help researchers better understand cancer tumors in humans. That’s because similar hormones appear to be involved in triggering the runaway cell replication that causes certain kinds of cancers, such as breast, ovarian, prostate, and testicular cancer. By learning to tinker with the hormonal pathways, the authors suggest, doctors might one day be able to prevent mouse-sized tumors from reaching elephantine proportions.