Species-specific sensitivity to TGFβ signaling and changes to the Mmp13 promoter underlie avian jaw development and evolution

Developmental control of jaw length is critical for survival. The jaw skeleton arises from neural crest mesenchyme and previously we demonstrated that these progenitors upregulate bone-resorbing enzymes includingMatrix metalloproteinase 13(Mmp13)when generating short quail beaks versus long duck bills. Inhibiting bone resorption orMmp13increases jaw length. Here, we uncover mechanisms establishing species-specific levels ofMmp13and bone resorption. Quail show greater activation of, and sensitivity toTransforming Growth Factor-Beta(TGFβ) signaling than duck; where mediators like SMADs and targets likeRunx2,which bindMmp13, become elevated. Inhibiting TGFβ signaling decreases bone resorption. We discover a SMAD binding element in the quailMmp13promoter not found in duck and single nucleotide polymorphisms (SNPs) near a RUNX2 binding element that affect expression. Switching the SNPs and SMAD site abolishes TGFβ-sensitivity in the quailMmp13promoter but makes duck responsive. Thus, differential regulation of TGFβ signaling andMmp13promoter structure underlie avian jaw development and evolution.