UCSF

How does form arise during development and change during evolution? How does form relate to function, and what enables structures of embryos to presage their later use in adults? To address these questions, we leverage the distinct functional morphology of the jaw in duck, chick, and quail. Duck develop secondary cartilage at the tendon insertion of their jaw adductor muscle on the mandible. An equivalent cartilage is absent in chick and quail. We hypothesize that species-specific jaw architecture and mechanical forces promote secondary cartilage in duck through differential regulation of FGF and TGFβ signaling. First, we examine the role of neural crest mesenchyme (NCM), which produces all jaw skeletal and connective tissues, in establishing species-specific pattern by transplanting NCM from chick to duck. Second, we investigate links between jaw architecture and mechanical forces by examining motility and by using finite element modeling. Third, we utilize loss-of-function approaches to determine whether candidate signaling mechanisms like voltage-gated ion channels and FGF or TGFβ signaling are required for secondary cartilage induction. Fourth, we perform gain-of-function experiments to determine whether FGF and TGFβ signaling are sufficient to induce chondrogenesis. Fifth, we quantified FGF and TGFβ pathway member expression in paralyzed and control samples to pinpoint potential mechanically regulated target genes. Our results provide insights on mechanisms linking musculoskeletal form and function during development, disease, and evolution.