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Cholesterol gets 'thumbs up' for role in digit development

When a new mother counts her newborn's fingers and toes, she probably doesn't realize that cholesterol may be to thank for baby's complete set of 20 digits.

Although cholesterol has a bad rap as the sticky, fatty substance responsible for clogging arteries, Vanderbilt University Medical Center researchers recently found that the attachment of cholesterol to an important developmental protein controls the development of fingers and toes in mice. Without cholesterol, mice developed extra digits, as well as digits in the wrong places.

The new study published online in the Proceedings of the National Academy of Sciences (PNAS) last week helps to clear up some of the conflicting data about cholesterol's controversial role in limb development, said senior author on the study, Chin Chiang, Ph.D., associate professor of Cell and Developmental Biology.

The developmental protein at work here, named Sonic hedgehog after the video game character, was discovered in the early 1990s and shown to have important roles in patterning the developing embryo, including proper digit patterning.

Chiang led the early studies showing that mice without Sonic hedgehog developed only a single digit â? a thumb on the front paw (or a "big toe"on the back paw).

The Sonic hedgehog protein is produced by a specialized group of cells located at the posterior part of the developing limb bud, which eventually develops into the pinkie finger or toe. At the site of its synthesis, Sonic hedgehog concentrations are high. It then diffuses out across the developing limb bud, and the declining concentrations (or gradient) of the protein dictate the identity of the other digits.

"Questions have remained about what regulates the Sonic hedgehog gradient,"said Chiang. "And we've been working on that for a number of years."

One clue about this regulation came when other researchers discovered Sonic hedgehog's rather unusual requirement â? the protein had
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Source:Vanderbilt University Medical Center


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