Genetic analysis of molecular oscillators in mammalian somitogenesis: clues for studies of human vertebral disorders.
The repeating pattern of the human vertebral column is shaped early in development, by a process called somitogenesis. In this embryonic process, pairs of mesodermal segments called somites are serially laid down along the developing neural tube. Somitogenesis is an iterative process, repeating at regular time intervals until the last somite is formed. This process lays down the vertebrate body axis from head to tail, making for a progression of developmental steps along the rostral-caudal axis. In this review, the roles of the Notch, Wnt, fibroblast growth factor, retinoic acid and other pathways are described during the following key steps in somitogenesis: formation of the presomitic mesoderm (PSM) and establishment of molecular gradients; prepatterning of the PSM by molecular oscillators; patterning of rostral-caudal polarity within the somite; formation of somite borders; and maturation and resegmentation of somites to form musculoskeletal tissues. Disruption of somitogenesis can lead to severe vertebral birth defects such as spondylocostal dysostosis (SCD). Genetic studies in the mouse have been instrumental in finding mutations in this disorder, and ongoing mouse studies should provide functional insights and additional candidate genes to help in efforts to identify genes causing human spinal birth defects.
Sewell
William
W
School of Life Sciences, Arizona State University, Tempe, Arizona 85287-4501, USA.
Kusumi
Kenro
K
D000818:Animals; D001683:Biological Clocks / Q000235:genetics*; D019521:Body Patterning; D004413:Dysostoses; D047108:Embryonic Development; D005346:Fibroblast Growth Factors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D051880:Receptors, Notch; D015398:Signal Transduction; D019170:Somites; D013122:Spinal Diseases / Q000235:genetics*; D013131:Spine / Q000196:embryology*; D014212:Tretinoin / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics
D051880:Receptors, Notch; D051153:Wnt Proteins; D014212:Tretinoin; D005346:Fibroblast Growth Factors