Experiments point to new theory of skeletal development

MADISON - Curious children and developmental biologists have long pondered the question: what makes a thumb a thumb and a pinkie a pinkie? The answer University of Wisconsin Medical School researchers have found may force scientists to revise their theories of how cells of the developing skeleton organize into exquisitely patterned tissue, from fingers to spines.

In various microsurgical experiments on the developing toes of chicken embryos still in the egg, the researchers discovered that the future uniqueness of each budding embryonic digit is determined by the webbed tissue located next to it. Until now, scientists considered this interdigital tissue, which disappears before birth, to be of little importance. It was interesting mainly because in most species it is eliminated by programmed cell death in order to free digits from one another.

"We were very surprised to find that developing cartilage, which eventually forms the skeleton, gets the information about what it will ultimately look like from surrounding soft tissue," said John Fallon, UW Medical School Harland Winfield Mossman Professor of Anatomy. "The general thinking has been that embryonic cartilage, digits and limbs are self-differentiating systems that develop independently."

Fallon and graduate student Randall Dahn report the find in the current (July 21) issue of Science.

In their experiments, they also found that specific levels of a substance called bone morphogenic protein (BMP), which is produced by interdigital web cells, plays a crucial role in determining the distinct characteristics, or identity, of each digit.

The UW team set out to test the existing, decades-old theory of how a developing digit learns that it is destined to become, for example, a big toe. According to the theory, a gene called Sonic hedgehog somehow gives each precursor digit detailed instructions about its particular identity. The developing tissue follows through on the cue days later, afte

Contact: Dian Land
University of Wisconsin-Madison

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