The trunk is built segment-by-segment by somites: paired blocks of paraxial mesoderm that bud off the unsegmented presomitic mesoderm in a strict head-to-tail sequence between weeks 3 and 5. Each somite gives rise to one vertebra (its bone and the disc above it), the corresponding rib, the segmental skeletal muscle, and the dermis of that level. When somite formation, segmentation, or resegmentation fails, the result is a recognizable spinal-axis malformation: hemivertebrae, butterfly vertebrae, block vertebrae, or fused ribs, and clinically, congenital scoliosis.
A clinical presentation pairing congenital scoliosis with hemivertebrae points to defective somite segmentation. Other embryologic processes (neural crest, notochord, neuropore) produce different phenotypes.
- Source tissue: paraxial mesoderm, lateral to the notochord and neural tube.
- Timing: a new pair of somites pinches off every ~90 minutes (in humans), 42–44 pairs total. Numbering: 4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 8–10 coccygeal (most coccygeal regress).
- The clock: oscillating expression of NOTCH-pathway genes (HES7, LFNG [lunatic fringe], DLL3, and MESP2) sets the segmentation period. Mutations in any of these break the clock and produce spondylocostal dysostosis (multiple hemivertebrae and rib anomalies, short trunk, normal limbs, normal intelligence).
- The wavefront: an FGF/WNT gradient (high posterior, low anterior) defines where the next somite will form. As the embryo elongates, the wavefront retreats and the clock fires again.
Each somite differentiates into three regions:
- Sclerotome (medial-ventral): bone and cartilage. Forms the vertebra and rib.
- Myotome (dorsolateral): skeletal muscle of the trunk and limbs at that level.
- Dermatome (most lateral): the dermis of the back. (The dermis of limbs and ventrum derives from lateral plate mesoderm.)
A single vertebra is not the descendant of a single somite. During week 4, each sclerotome splits into a cranial half and a caudal half. The caudal half of one sclerotome fuses with the cranial half of the next to form a vertebral body. This shift (von Ebner's law of resegmentation) is what allows segmental nerves and muscles, which stayed with the original somite, to bridge across vertebrae rather than being trapped within a single bone.
Consequences:
- Hemivertebra: failure of one half-sclerotome to develop. The remaining wedge produces lateral spinal curvature → congenital scoliosis.
- Butterfly vertebra: failure of the two lateral chondrification centers to fuse across the midline (notochord-related). Common as an incidental finding; classic in Alagille syndrome.
- Block vertebra: failure of resegmentation between two sclerotomes; adjacent vertebrae fuse. Klippel-Feil syndrome at the cervical level.
- Sagittal cleft / butterfly: persistence of notochord remnant within the vertebral body.
The notochord doesn't form vertebrae itself; once the sclerotomes engulf it, the notochord regresses and persists only as the nucleus pulposus of each intervertebral disc. The annulus fibrosus comes from sclerotome. Persistent notochordal tissue gives rise to chordomas, midline tumors of the clivus and sacrum.
- Spondylocostal dysostosis (SCD): mutations in NOTCH-pathway clock genes (DLL3, MESP2, LFNG, HES7, TBX6). Multiple hemivertebrae, fused/missing ribs ("crab-like" rib pattern on X-ray), short trunk, normal cognition. Autosomal recessive (most types).
- Spondylothoracic dysostosis (Jarcho-Levin): MESP2; severe trunk shortening with respiratory compromise. Restricted to certain populations (Puerto Rican).
- Klippel-Feil syndrome: failed cervical segmentation; short neck, low hairline, restricted neck motion. Usually sporadic; some familial forms map to GDF6, GDF3, MEOX1.
- VACTERL association: sporadic, multifactorial; Vertebral defects (often hemivertebrae) + Anal atresia + Cardiac + Tracheo-Esophageal fistula + Renal + Limb. Diagnosis requires ≥3 features.
- Alagille syndrome: JAG1 (NOTCH ligand) or NOTCH2 mutation; butterfly vertebrae + bile duct paucity + posterior embryotoxon + pulmonary stenosis + characteristic facies.
| Failure | Resulting malformation |
|---|---|
| Half-sclerotome fails to develop | Hemivertebra → congenital scoliosis |
| Resegmentation fails between two sclerotomes | Block vertebra (Klippel-Feil if cervical) |
| Lateral chondrification centers fail to fuse | Butterfly vertebra (Alagille classic) |
| Multiple segmentation failures (clock genes) | Spondylocostal dysostosis |
| Caudal somitogenesis fails entirely | Caudal regression / sacral agenesis (diabetic embryopathy) |
| Notochord remnant persists | Chordoma; sometimes vertebral cleft |
"DELiver MESs HEra": clock genes for spondylocostal dysostosis. DLL3, LFNG, MESP2, HES7. (Plus TBX6.)
"Sclerotome → Skeleton": the medial-ventral somite half makes bone. The other halves make muscle (myotome) and back skin (dermatome).
- Hemivertebra + congenital scoliosis = somite segmentation defect. This points to defective somite segmentation rather than a neural crest or notochord process.
- One vertebra = caudal half of somite N + cranial half of somite N+1. This is why a segmental nerve exits between two vertebrae rather than through one.
- NOTCH = clock. Any clock-gene mutation produces multiple-level vertebral and rib anomalies, not isolated single-level defects.
- Diabetic embryopathy hits the caudal somites hardest → sacral agenesis / caudal regression. The cranial somites (cervical, thoracic) are usually spared.
- Butterfly vertebra in a child with cholestasis and pulmonary stenosis → Alagille (JAG1).