Notochord: morphogenesis, structure, and functional significance

The notochord represents a defining synapomorphy of the phylum Chordata, serving as the primary axial skeleton and a crucial embryonic organizer. This review systematizes current concepts regarding the evolutionary origin, molecular mechanisms of morphogenesis, and structural–functional organization of the notochord. Major evolutionary hypotheses — dorsoventral inversion and aboral dorsalization — are examined and compared in the context of vertebrate body plan formation. The hierarchical gene regulatory network underlying notochord development is described in detail, with emphasis on the central role of the transcription factor TBXT (Brachyury) and the Wnt/PCP, Hedgehog, and Notch signaling pathways. Molecular and cellular mechanisms of convergent extension, formation of the perinotochordal sheath, and cellular vacuolization — processes that generate turgor pressure and mechanical stiffness — are analyzed. Particular attention is given to notochord formation in humans, from the stage of the notochordal plate to its postnatal transformation into the nucleus pulposus of the intervertebral discs. The clinical relevance of residual progenitor cell populations within the nucleus pulposus expressing the markers Tie2 and GD2 is discussed. Their role in maintaining homeostasis within the avascular intervertebral disc, the association between depletion of this cell pool and the development of degenerative spinal disorders, and their potential applications in regenerative medicine are considered. The review also addresses issues related to the molecular diagnosis of chordoma as a tumor of notochordal origin.