The findings, published in Current Biology Oct. 4, identify a gene that plays a central role in the evolution of limb development in vertebrates. By manipulating this gene in mice, researchers were able to activate an ancestral form of limb development seen in early tetrapods (four-legged vertebrates).
In the limbs of all tetrapods, the bones on the hands and feet on the outside edge form first, known as postaxial development. The study focuses on salamanders, which are the only exception to this rule: their limb bones develop preaxially, or from the inside edge; the thumb before pinky.
In both mice and axolotl salamanders, researchers manipulated the function of Gli3, a gene that is known to be important in regulating the pattern of limb development. Mice with excess GLi3 repressor activity reverted to preaxial limb development — just like salamanders. Conversely, when Gli3 was “knocked out” in salamanders, they developed limbs postaxially, like the mice and all other tetrapods.
Journal Reference: Anna Trofka, Bau-Lin Huang, Jianjian Zhu, William F. Heinz, Valentin Magidson, Yuki Shibata, Yun-Bo Shi, Basile Tarchini, H. Scott Stadler, Mirindi Kabangu, Nour W. Al Haj Baddar, S. Randal Voss, Susan Mackem. Genetic basis for an evolutionary shift from ancestral preaxial to postaxial limb polarity in non-urodele vertebrates. Current Biology, 2021; DOI: 10.1016/j.cub.2021.09.010