Limbs have a proximodistal axis that usually is not apparent early in development, a striking example of epigenesis. The proximodistal axis was the subject of experimental and theoretical study before any molecular genetic understanding emerged. As developmental genetic studies in Drosophila advanced, the descriptive polar coordinate model of the 1970s evolved into an understanding of how preexisting developmental compartments interact to express signaling molecules, including Hedgehog, Wingless, and Decapentaplegic, and how these define a proximodistal axis as limbs appear.
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