Title: Investigating Novel Gene Function and Mechanotransduction in Vertebrate Tendon Development
Abstract: Cells regularly experience physical stressors such as mechanical force and respond to them using a variety of biological processes and signaling pathways. How specialized cells not only sense force, but change their tissue environment to adapt to these perturbations is not well known. An excellent example of force dependent tissue morphogenesis is in the development of the tendon tissue in the vertebrate embryo. Tendon producing fibroblasts, called tenocytes, respond to pulling forces generated by muscular contraction by upregulating various extracellular matrix (ECM) proteins which constitute the bulk of the tendon tissue itself. In fact, our lab has shown requirements for muscular contraction to facilitate proper tendon formation and organization in the developing zebrafish embryo. The earliest embryonic developmental marker for the Mesenchymal Stem Cell (MSC) to tenocyte differentiation process is Scleraxis (Scx), a transcription factor (TF) protein found to be downstream of the force-responsive tenocyte differentiation pathway (Subramanian and Schilling 2015). Force-dependent tenocyte Scx activation leads to upregulation and secretion of structural proteins (e.g. collagen) and maintenance-related proteoglycans into the ECM environment. Despite the importance of mechanical stress in tendon morphogenesis, little is known about the roles and modes of action of proteins that sense and/or transmit cellular responses to these signals to regulate their environment, such as Scx. Our preliminary data suggest multiple novel gene targets currently understudied in the tendon mechanobiology literature (especially in vivo), as well as a new mechanism of nuclear transport for Scx to direct transcription of various ECM proteins important for tendon development.