somites

**Formation:** During gastrulation and neurulation (week 3), the paraxial mesoderm segments in a cranial-to-caudal sequence into somitomeres and then somites, which flank the neural tube and notochord. About 3-4 pairs form per day, giving roughly 42-44 pairs by the end of week 5 (4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 8-10 coccygeal, with the first occipital and the last 5-7 coccygeal somites regressing). Somite number is a way to estimate embryonic age early in development.

**Regulation:** - The segmentation clock is an oscillating gene expression system (Notch/Delta, Hes/Her genes) that works with the FGF8 and Wnt gradients (caudal to rostral) and the retinoic acid gradient (rostral to caudal) to set somite boundaries. - Hox genes specify the regional identity of vertebrae. Hox mutations cause homeotic transformations (for example, a lumbar vertebra that resembles a thoracic one). - Notch pathway defects (DLL3, MESP2, LFNG mutations) cause spondylocostal dysostosis, with segmentation defects of the vertebrae and ribs.

**Derivatives:** - *Sclerotome* (ventromedial): vertebral bodies, intervertebral discs (the annulus fibrosus; the nucleus pulposus comes from the notochord), and ribs. Controlled by Shh and Noggin from the notochord and floor plate, which induce Pax1 and Pax9. - *Myotome*: skeletal muscle. The epaxial division (innervated by dorsal primary rami) forms the deep back muscles (erector spinae). The hypaxial division (innervated by ventral primary rami) forms the body wall and limb muscles. - *Dermatome* (dermomyotome, dorsolateral): dermis of the back. Controlled by Wnt and Neurotrophin-3 from the neural tube, which induce Pax3 and Pax7. - Somites also give rise to the vasculature (endothelial cells) and tendons (syndetome).

**Clinical correlates:** - Neural tube defects and vertebral defects, such as spina bifida occulta (failure of the vertebral arches to fuse) and spina bifida cystica. - Klippel-Feil syndrome: fusion of cervical vertebrae causing a short neck and low hairline. - Hemivertebrae and congenital scoliosis from abnormal somite segmentation. - VACTERL association: vertebral anomalies are one component. - Prune belly syndrome and congenital absence of abdominal wall muscle reflect abnormal hypaxial myotome development. - Poland syndrome: absence of the pectoralis muscle. - Segmental (dermatomal) innervation reflects somite origin. Dermatomes and myotomes retain their spinal nerve supply as they migrate. - Maternal diabetes and valproate exposure are associated with vertebral and neural tube defects. - Retinoic acid (isotretinoin) teratogenicity affects Hox gene expression and patterning.

**High-yield pearls:** Somites come from paraxial mesoderm. The intermediate mesoderm forms the urogenital system, and the lateral plate mesoderm forms the body wall, serous membranes, and limb connective tissue. The notochord induces the neural plate and sclerotome. Somite-derived muscle cells (myoblasts) migrate into the limbs and body wall, while limb bone and tendons come mostly from the lateral plate mesoderm.