Appendicular skeleton develops from a single cartilaginous unit through the process known as endochondral ossification. In my doctoral thesis, I studied endochondral ossification and elucidated the roles of multiple genes invovled in skeletal differentiation.

 

I identified Barx1, a homeo-domain containing transcription factor, as a candidate regulator of interzone formation and articular joint initiation in the developing appendicular skeletal cartilage. (Link to publication)

 

In my second project, I found Prdx1, a known ROS scavenger protein, to have a role in the maintenance of pre-hypertrophic state of cartilage cells. Pre-hypertrophy is a necessary prerequisite for subsequent hypertrophic differentiation of cartilage cells and bone formation. (Link to publication)

 

Finally, I show that Dpysl3, a BMP pathway downstream target, is involved in bone formation through its role in maintaining central stress fibers in bone cells. Loss of Dpysl3 perturbs endochondral bone formation, connecting bone formation with proper cytoskeletal assembly. (Link to conference proceedings)

 

In summary, my doctoral work revealed three new candidates involved in three separate stages of endochondral ossification and therefore development of appendicular bones.