BIG flies, small flies鈥攖heir cells are all the same size, right? Not
necessarily. Miniflies made of tiny cells have got biologists puzzling over how
animals control their size. They have also suggested a new battle plan in the
fight against cancer.
Some neurons and muscle cells in a Great Dane, for instance, are
significantly larger than those in a cocker spaniel. But most of the cells in
the two breeds are the standard size鈥攖he larger dog simply has more of
them.
What isn鈥檛 clear is how each cell 鈥渒nows鈥� that there has been enough growth
and replication to make an animal of normal size. 鈥淣o one has any idea yet of
how cells sense that,鈥� says George Thomas, a developmental biologist at the
Friedrich Miescher Institute in Basel, Switzerland. Even when biologists have
used genetic trickery to shrink cells in fruit flies or make them larger in
salamanders, the resulting animals were the usual size, but simply had more or
fewer cells than normal.
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But another kind of genetic engineering has thrown up a different result.
Thomas and his team were breeding flies with a mutation in a gene that produces
S6 kinase, an enzyme the fly needs to respond to a particular growth factor.
They found that the mutant flies had cells that were just two-thirds the normal
size.
The researchers thought the insects would simply compensate by producing more
cells to reach the same bulk. But instead, the mutant flies had exactly the same
number of cells, so they were tiny and weighed about half as much as a normal
fly (Science, vol 285, p 2126). 鈥淓verything in the fly is perfectly in
proportion, just smaller,鈥� says Thomas.
Martin Raff, an expert on animal development at University College London,
suspects S6 kinase is involved in helping cells sense the total cell mass in
flies. Without it, they can only control size by counting the number of cells.
鈥淲hat it really emphasises is how little we still know,鈥� he says. 鈥淭his
experiment should catalyse a lot of interest in the field.鈥�
Thomas also found that the S6 kinase mutation not only shrinks cells and
reduces overall bulk, but also slashes cell growth rate. These properties
suggest that blocking S6 kinase could help prevent the growth of cancer cells.
Already the National Cancer Institute near Washington DC is coordinating
clinical trials of a drug that blocks a protein that activates S6 kinase. Thomas
speculates that molecules targeting S6 kinase directly could be even more
potent.