Transient agonism of the sonic hedgehog pathway triggers a permanent transition of skin appendage fate in the chicken embryo.

Vertebrate skin appendage early development is mediated by conserved molecular signaling composing a dynamical reaction-diffusion-like system. Variations to such systems contribute to the remarkable diversity of skin appendage forms within and among species. Here, we demonstrate that stage-specific transient agonism of sonic hedgehog (Shh) pathway signaling in chicken triggers a complete and permanent transition from reticulate scales to feathers on the ventral surfaces of the foot and digits. Resulting ectopic feathers are developmentally comparable to feathers adorning the body, with down-type feathers transitioning into regenerative, bilaterally symmetric contour feathers in adult chickens. Crucially, this spectacular transition of skin appendage fate (from nodular reticulate scales to bona fide adult feathers) does not require sustained treatment. Our RNA sequencing analyses confirm that smoothened agonist treatment specifically promotes the expression of key Shh pathway-associated genes. These results indicate that variations in Shh pathway signaling likely contribute to the natural diversity and regionalization of avian integumentary appendages.