Distinct global shifts in genomic binding profiles of limb malformation-associated HOXD13 mutations

Some effects on cell differentiation and development are shared between Hoxd13^Q317K and PITX1. (Upper row) Eosin-stained chMM cultures for Hoxd13^wt, Hoxd13^Q317R, Hoxd13^Q317K, and PITX1. Both Hoxd13^Q317K and PITX1 induced differentiation into thick, fibrotic tissue. (Lower row) Viral overexpression of Hoxd13^wt, Hoxd13^Q317R, Hoxd13^Q317K, and PITX1 in chicken wing buds (HH36). Hoxd13^wt and Hoxd13^Q317R overexpression leads to an overall shortening of skeletal elements. Hoxd13^Q317K-infected wing buds lack or have a reduced forelimb-specific patagium, have a straightened wrist, and develop a fourth digit (arrowheads). PITX1 overexpression leads to a partial hind- to forelimb transformation.