The development, degeneration and tumorigenesis of the notochord

The notochord is a transient embryonic structure with two distinct postnatal fates. While most notochord cells are compressed into the intervertebral disc to form the nucleus pulposus (NP), incomplete regression leaves remnants in the vertebral body that may serve as chordoma precursors. From this "shared notochord lineage" perspective, this review integrates the regulatory mechanisms governing notochord development, NP formation, and chordoma tumorigenesis. We focus on how the mechanical force-YAP signaling axis and the Shh signaling network coordinately regulate notochord cell fate, and how the aberrant reactivation of these developmental pathways (e.g., brachyury, YAP) drives malignant transformation in chordoma. By bridging embryonic development and cancer biology, this review provides a unified conceptual framework that informs emerging targeted therapies and precision subtyping strategies for chordoma. This integrated perspective highlights how notochord biology determines cell fate and tumorigenesis across these distinct but interrelated contexts.