Notochordal Morphogenesis and the Origin of Chordoma

Chordomas are locally aggressive, slow-growing tumors. Typically found in the axial skeleton, they are thought to be derived from notochord remnants. The notochord is a critical midline structure present in the early weeks of embryogenesis, where it plays a critical role in left-right and local tissue development. While the nucleus pulposus of the intervertebral disk appears to be derived from the primitive notochord, remnant notochordal cells can be found throughout adult vertebrae. What drives the transition from remnant notochord cell to chordoma remains elusive, and is likely multifactorial, but the expression of the brachyury gene appears central to this process. While wide resection remains the gold standard when possible (with or without radiation), these difficult-to-treat tumors have a high local recurrence rate even when appropriate margins appeared to have been achieved. By better understanding the role of the notochord and notochordal morphogenesis in the origins of chordomas, more efficacious, targeted therapies are currently being developed.