Genetic basis for an evolutionary shift from ancestral preaxial to postaxial limb polarity in non-urodele vertebrates

In most animals with limbs, the posterior side of the limb develops slightly before the anterior. Salamanders are an exception: the anterior side develops first. The genetic reason for this difference was unknown. This study found that a gene called Gli3 plays a key role. In mice, increasing the activity of Gli3 causes the limbs to develop like salamanders. Conversely, reducing Gli3 activity in axolotls causes their limbs to develop like other animals. This suggests that changes in Gli3 activity were important in the evolution of limb development.

• 1
  Deletion of 5’Hoxd genes in mice leads to preaxial dominant limb formation, an ancestral trait.
• 2
  Elevated Gli3 repressor activity causes preaxial dominance in mice, while Gli3 removal restores postaxial dominance in 5’Hoxd mutants.
• 3
  Knockdown of Gli3 in axolotl shifts limb skeletal formation to postaxial dominance and results in polydactyly.