The notochord is a flexible, rod-like structure composed of mesodermal cells that forms temporarily within the human embryo. This transient structure is a defining feature of the phylum Chordata, providing the initial central structural support along the midline of the developing body. Although it disappears as a distinct organ during early development, the notochord acts as an organizer. Its signaling activity guides the proper formation and patterning of surrounding tissues, including the entire nervous system and axial skeleton.
Formation During Early Embryogenesis
The formation of the notochord is linked to gastrulation, a reorganization of the embryo occurring during the third week of human gestation. Gastrulation begins with the primitive streak, which establishes the embryo’s head-to-tail and left-right orientation. Cells from the epiblast layer migrate inward through the primitive node. These migrating cells travel cranially along the midline to form the notochordal process, initially a hollow tube.
Notochordal Transformation
The notochordal process embeds itself between the ectoderm and the endoderm, forming the temporary notochordal plate. The plate then folds and detaches from the endoderm, transforming into the definitive, solid notochord. This rod of cells is situated in the mesoderm layer, positioned directly beneath the developing nervous system. This sequence, from cell migration to solid notochord formation, occurs rapidly during the third and fourth weeks, ensuring the structure is in place to guide subsequent organ formation.
Defining the Body Axis and Nervous System Development
The notochord performs two primary functions: providing mechanical support and acting as a signaling center. Mechanically, it serves as the embryo’s first axial skeleton, offering rigidity and flexibility for the early folding of the embryo. This central position establishes the longitudinal axis around which the rest of the body plan is organized.
Signaling and Neurulation
The notochord orchestrates the development of the nervous system through molecular communication. It secretes the protein Sonic Hedgehog (Shh), which diffuses upward to the overlying ectoderm. The concentration gradient of Shh induces the formation of the neural plate, a process called neurulation, which folds to become the neural tube. The neural tube is the precursor to the brain and spinal cord.
Vertebral Formation
The Shh signaling gradient also determines the cell types within the ventral part of the neural tube, specifying the development of the floor plate and motor neurons. Concurrently, Shh regulates the fate of the surrounding mesoderm destined to form the vertebrae. This signaling instructs the adjacent mesoderm to condense and differentiate into the vertebral bodies, positioning them precisely around the neural tube.
The Adult Legacy: Nucleus Pulposus
Following its roles in patterning and induction, the notochord largely regresses and is incorporated into the forming axial skeleton. The persistent notochordal cells transform to become the nucleus pulposus, the gelatinous core of the intervertebral discs. This remnant is centrally located within each disc, surrounded by the fibrous annulus fibrosus. The nucleus pulposus acts as a central pivot point, allowing the disc to withstand compressive forces. Its high water content and viscoelastic properties distribute pressure evenly and enable spinal flexibility. The notochordal cell lineage remains the source of this shock-absorbing tissue throughout life, even as the cells decrease in number and change morphology over time.
Pathological Outcomes and Clinical Significance
A failure in the normal regression or signaling of the notochord can lead to specific developmental defects and rare cancers. Disrupted inductive signals can result in errors in vertebral segmentation, leading to malformations of the spinal column. These errors highlight the coordination required between notochord signaling and the surrounding mesoderm to form properly shaped vertebrae.
Chordoma
When notochordal remnants fail to regress and undergo malignant transformation, they can give rise to a rare, slow-growing bone tumor called a chordoma. Chordomas typically occur along the axial skeleton, commonly found at the base of the skull (clivus) or in the sacrococcygeal region of the lower spine. This location mirrors the anatomical path of the embryonic notochord. These tumors are characterized by large, vacuolated cells, known as physaliphorous cells, and their presence serves as a direct clinical manifestation of persistent notochordal tissue.