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

Abstract

Precise developmental control of jaw length is critical for survival, but underlying molecular mechanisms remain poorly understood. The jaw skeleton arises from neural crest mesenchyme (NCM), and we previously demonstrated that these progenitor cells express more bone-resorbing enzymes including <i>Matrix metalloproteinase 13</i> (<i>Mmp13</i>) when they generate shorter jaws in quail embryos versus longer jaws in duck. Moreover, if we inhibit bone resorption or <i>Mmp13,</i> we can increase jaw length. In the current study, we uncover mechanisms establishing species-specific levels of <i>Mmp13</i> and bone resorption. Quail show greater activation of and sensitivity to transforming growth factor beta (TGFβ) signaling than duck; where intracellular mediators like SMADs and targets like <i>Runt-related transcription factor 2</i> (<i>Runx2</i>)<i>,</i> which bind <i>Mmp13</i>, become elevated. Inhibiting TGFβ signaling decreases bone resorption, and overexpressing <i>Mmp13</i> in NCM shortens the duck lower jaw. To elucidate the basis for this differential regulation, we examine the <i>Mmp13</i> promoter. We discover a SMAD-binding element and single nucleotide polymorphisms (SNPs) near a RUNX2-binding element that distinguish quail from duck. Altering the SMAD site and switching the SNPs abolish TGFβ sensitivity in the quail <i>Mmp13</i> promoter but make the duck promoter responsive. Thus, differential regulation of TGFβ signaling and <i>Mmp13</i> promoter structure underlie avian jaw development and evolution.