Somitogenesis is a fundamental process in the early development of vertebrates, where segmented blocks of tissue, known as somites, form in a rhythmic pattern along the embryonic axis. These transient structures are bilaterally paired and arise from the paraxial mesoderm, a specific region of embryonic tissue. The formation of somites is a highly organized process that establishes the basic segmented body plan of all vertebrates, laying the groundwork for many of the body’s future structures.
The Rhythmic Process of Somite Formation
The formation of somites is precisely controlled by a molecular mechanism often referred to as the “segmentation clock”. This internal oscillator drives the periodic budding off of new somites from the presomitic mesoderm (PSM), which is located at the posterior end of the developing embryo. The pace of this clock is species-specific, with new pairs of somites forming every 90 minutes in chick embryos, every 2 hours in mice, and every 30 minutes in zebrafish.
Waves of gene expression, involving key signaling pathways like Notch, Wnt, and FGF (Fibroblast Growth Factor), orchestrate this rhythmic process. The FGF pathway, for instance, establishes a gradient of signaling that influences cell maturation and helps determine the position of somite boundaries. This gradient moves posteriorly as the embryo elongates, linking somite size to the overall growth of the embryo.
The Notch signaling pathway also plays a significant role, with its activity triggering a genetic cascade that leads to the morphological changes associated with new somite formation. Specifically, Notch activates genes like Mesp2 in a precise domain anterior to the determination front, a region where cells are committed to forming a somite. This intricate interplay ensures that somites form in a sequential, head-to-tail direction.
After the initial budding, the newly formed somite undergoes a transformation called epithelialization. Initially, the cells in the presomitic mesoderm exist as a loose mesenchymal aggregate. These cells then reorganize and transform into a distinct epithelial sphere, forming clear boundaries between individual somites. This process involves the increased expression of adhesion molecules like E-cadherin, which helps cells localize appropriately and establish the new somite boundary.
From Somites to Specialized Tissues
Once formed, somites do not remain as undifferentiated blocks; instead, they undergo a process of differentiation, subdividing into distinct components that contribute to various specialized tissues throughout the body. Each somite differentiates into three primary parts: the sclerotome, the myotome, and the dermatome. This differentiation is a crucial step in laying out the segmented body plan.
The sclerotome, located in the ventromedial part of the somite, is responsible for forming the skeletal components of the axial body. Cells from the sclerotome migrate to surround the neural tube and notochord, giving rise to the vertebrae and ribs. The sclerotome from the inferior portion of one segment will merge with the superior portion of the adjacent somite to form a single vertebra, a process known as resegmentation.
The myotome, which develops from the inner part of the somite, is the precursor to most of the skeletal muscles of the trunk and limbs. It further divides into two regions: the epimere, which forms the deep back muscles (paraspinal muscles), and the hypomere, which develops into the muscles of the body wall, including abdominal and limb muscles. This ensures the segmented organization of musculature along the body axis.
Finally, the dermatome, located in the outer region of the somite, differentiates to form the dermis of the back. While the dermis of the limbs originates from a different embryonic layer, the dermatome specifically contributes to the skin on the dorsal side of the body. The coordinated migration and differentiation of these somite derivatives are fundamental for the proper construction of the vertebrate body, including the spinal column, associated muscles, and segments of the skin.
When Somite Development Goes Wrong
The precise timing and formation of somites are highly regulated processes; therefore, any disruptions or errors during somitogenesis can lead to significant congenital anomalies, particularly affecting the vertebral column. These developmental issues underscore the importance of accurate somite formation for a healthy body plan. Such defects are estimated to affect between 0.5 and 1 newborn per 1000 births.
One common consequence of disrupted somitogenesis is congenital scoliosis, a condition characterized by an abnormal lateral curvature of the spine exceeding 10 degrees. This can result from malformations like hemivertebrae, where only half of a vertebra forms, or block vertebrae, where adjacent vertebrae fuse abnormally. Mutations in genes involved in the segmentation clock, such as DLL3, have been linked to severe conditions like Spondylocostal Dysostosis (SCD), which involves extensive hemivertebrae, abnormally aligned ribs, and a shortened trunk.
While vertebral column defects are prominent, severe compromises in somite formation can also have broader implications for muscle and dermal development. For example, mutations in clock genes can lead to muscle fiber disorganization and reduced muscle volume, which may contribute to conditions like scoliosis later in life, even with only mild vertebral changes. Environmental factors, such as hypoxia during pregnancy, can also increase the severity of vertebral defects, especially in embryos with certain genetic predispositions.