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The scientists used a technique that they crafted to identify the short period when a particular gene is turned on as a fetus develops. The tool may give clues to the cause of cleft palate and other birth defects in people.

The process that creates a complex, multicellular animal out of a single fertilized egg cell typically relies on the coordinated activity of thousands of genes. Individual genes must create proteins precisely when they’re needed, and the genes often turn on and off more than once during development.

Scientists have a variety of tools to investigate the roles that each gene plays throughout this process. However, most of those tools eliminate a gene or permanently shut off its activity early in development. Scientists can’t then tell at what time the gene’s activity becomes important.

“That’s a level of precision that we haven’t been able to achieve,” says Michael Longaker, a pediatric craniofacial surgeon at Stanford University School of Medicine in Palo Alto, Calif.

To gain more insight into the timing of gene activity, Longaker and his colleagues focused on a mouse gene called glycogen synthase kinase-3sz (GSK-3sz). Previous studies had linked this gene to palate and breastbone development.

The researchers engineered mice with a chemical tag on GSK-3sz that made the protein produced by this gene degrade rapidly. Like mice engineered to lack the gene, they developed cleft palates and malformed breastbones, and they died at birth.

However, the chemical tag was constructed so that a drug called rapamycin would prevent the GSK-3sz protein from degrading. When the researchers gave rapamycin throughout pregnancy to female mice carrying fetuses with the chemical tag, the babies were born healthy and didn’t show the typical birth defects.

To specify when fetuses need the GSK-3sz protein to develop normally, Longaker’s team gave rapamycin during a variety of 2-day stretches to groups of female mice carrying fetuses with the chemical tag. The researchers report in an upcoming Nature, published online on Feb. 11, that the GSK-3sz protein participates in palate development and breastbone formation at different times. Mice whose mothers were treated with the drug between 13.5 to 15 days after gestation were spared cleft palates, but normal breastbone development required treatment between days 15.5 to 17.

“This really nails down the windows when the gene is critical,” Longaker says.

Randall Peterson, a developmental biologist at Massachusetts General Hospital in Boston, calls the new technique “pretty exciting.” He says, “What you really want is the ability to test when specific genes are required and what roles they play at different times during development. This technique allows you to do that with decent temporal control.”

A better grasp of which genes are important at which times during development, Peterson adds, may eventually enable physicians to treat cleft palate and other birth defects before a baby is born. —C. BROWNLEE

Perils of
Migration
New evidence that bats
stalk birds

Big Mediterranean bats snatch migrating songbirds out of the night sky in spring and fall, according to a new study.

When researchers proposed that idea in 2001, “there was so much controversy,” says Ana Popa-Lisseanu of the Doñana Biological Station in Seville, Spain. Now, she and her colleagues have cooperated with the idea’s main critic, a conservation biologist at the University of Bern in Switzerland, to settle their argument.

The bats’ blood chemistry points to bird feasts during migration season, the former disputants now agree. Their joint study appears online in the February PLoS ONE.

Billions of birds travel across the Mediterranean region twice each year. Most migrants use what had seemed to be safe flyways hundreds of meters above ground at night.

Yet danger now appears to loom, although no scientist has reported seeing a bat snag a bird. In 2000, two researchers in Italy reported that droppings from the giant noctule bat (Nyctalus lasiopterus) contained bits of bird feathers. Debate flared the next year after the Doñana researchers also reported feathers in noctule droppings (SN: 8/11/01, p. 86).

In 2003, Bern conservation biologist Raphaël Arlettaz and a colleague published a contrary scenario: Stray feathers waft down from migrating birds, and bats mistake them for night-flying insects. “Feathers in droppings are no proof that you eat bird flesh but certainly [are proof ] that you swallow feathers,” says Arlettaz.

After Popa-Lisseanu joined the Seville group in 2003, it began looking for a good test of whether bats eat birds. The team decided to track the bat’s diet by measur-

NIGHT STALKER The giant noctule bat is more than a match for a migrating songbird that weighs as little as 6 grams. The bat’s wingspan can reach 45 centimeters, and the bat can weigh 50 gm.

ing the ratios of rare-but-stable forms to the common forms of carbon and nitrogen in the bats and their potential prey. Working with Arlettaz, the researchers established that the migrating birds have higher ratios of carbon-13 and nitrogen-15 than the local insects do.

For 2 years, the researchers periodically took blood samples from as many giant noctules as they could catch. Monthly numbers varied, for example, from 3 to 18 during spring, summer, and fall of 2003.

The isotope ratios in a bat’s blood change within a day to reflect what it’s eaten. In summer, the researchers found, the ratios stayed relatively low, indicating a regular insect diet. In spring, the ratios were a bit higher, and in fall, they jumped out of the insect-diet range.

The results support the idea that bats prey on migrating birds. To get the observed rise in isotope ratio, the bats must actually be digesting bird tissue, the researchers conclude.

“I was one of the major detractors,” says Arlettaz, “but with good evidence, I have now changed my mind completely. The most virulent detractors become the best proponents.”

Michael J. Ryan of the University of Texas at Austin, who has studied bats that eat frogs, says that the new finding “makes perfect sense, as long as the bats are big and the birds are small.” —S. MILIUS