somite

**Formation:** Paraxial mesoderm segments into somitomeres, which condense into somites in a cranial-to-caudal sequence. Somitogenesis begins around day 20 (week 3) and produces about 42-44 pairs by week 5. The first pair appears near the future occipital region. Somite count is a useful way to estimate embryonic age early in development. The "segmentation clock" drives the timing, with oscillating Notch, Wnt, and FGF signaling. Hox genes specify the regional identity of the vertebral levels.

**Differentiation (mnemonic: "SMD", from medial to lateral/ventral to dorsal):** - **Sclerotome** (ventromedial): Forms vertebrae, intervertebral discs (annulus fibrosus), and ribs. Induced by **Sonic hedgehog (SHH)** from the notochord and floor plate. Express **PAX1** and **PAX9**. - **Myotome**: Forms the skeletal muscle of the back (epaxial, from the dorsomedial portion, innervated by the dorsal primary rami) and the body wall and limbs (hypaxial, from the ventrolateral portion, innervated by the ventral primary rami). Expresses **MyoD** and **Myf5**. - **Dermatome** (dorsolateral): Forms the dermis of the back. Expresses **PAX3**. - Some texts also describe a **syndetome**, which forms tendons.

**Related structures:** - The notochord induces the nucleus pulposus of the intervertebral disc. The notochord itself is derived from the axial mesoderm (the notochordal process). - Each vertebra forms from the caudal half of one sclerotome and the cranial half of the next (**resegmentation**). As a result, myotomes bridge the intervertebral discs and can move the spine. Spinal nerves exit at the intervertebral foramina. - Somites do not form the head musculature. That comes from somitomeres and pharyngeal arch mesoderm. - The limb muscles come from hypaxial myotome cells that migrate into the limb buds. The limb dermis comes from lateral plate mesoderm.

**Clinical correlations:** - **Neural tube defects** (spina bifida occulta, meningocele, and myelomeningocele) involve failure of the vertebral arches (sclerotome derivatives) to fuse. Folate deficiency is a risk factor. - **Klippel-Feil syndrome**: Fusion of the cervical vertebrae from abnormal segmentation. It presents with a short neck, low posterior hairline, and limited neck motion. - **Congenital scoliosis**: Hemivertebrae or butterfly vertebrae from abnormal somite formation or segmentation. - **Spondylocostal dysostosis** (Jarcho-Levin): Mutations in Notch pathway genes (such as DLL3) cause vertebral and rib segmentation defects. - **VACTERL association**: Includes vertebral anomalies. - **Prune belly (Eagle-Barrett) syndrome** and **congenital absence of abdominal wall muscles** reflect abnormal myotome or hypaxial muscle development. - **Waardenburg syndrome (type I and III)** involves PAX3 mutations, which affect neural crest and somite derivatives. - **Dermatomes in clinical practice:** Each spinal nerve supplies a segmental skin area derived from its somite level (for example, C6 thumb, T4 nipple, T10 umbilicus, L1 inguinal ligament). Shingles (herpes zoster) follows a single dermatome.

**High-yield timeline:** Week 3 is the start of somitogenesis, with folding of the embryo and neurulation. This is the same time that the neural tube is forming, so it is a vulnerable period for axial skeleton and neural tube defects.