The long and short of it: Somite formation in mice

Abstract

A fundamental characteristic of the vertebrate body plan is its segmentation along the anterior-posterior axis. This segmental pattern is established during embryogenesis by the formation of somites, the transient epithelial blocks of cells that derive from the unsegmented presomitic mesoderm. Somite formation involves a molecular oscillator, termed the segmentation clock, in combination with gradients of signaling molecules such as fibroblast growth factor 8, WNT3A, and retinoic acid. Disruption of somitogenesis in humans can result in disorders such as spondylocostal dysostosis, which is characterized by vertebral malformations. This review summarizes recent findings concerning the role of Notch signaling in the segmentation clock, the complex regulatory network that governs somitogenesis, the genes that cause inherited spondylocostal dysostosis, and the mechanisms that regulate bilaterally symmetric somite formation. Developmental Dynamics 235:2330 -2336, 2006.

Anabolic actions of Notch on mature bone

“…Mutations of JAG1 and NOTCH2 in concert cause Alagille syndrome, marked by impaired craniofacial development due to somite segmentation defects. However, mice lacking individual Notch receptors are invariably lethal in utero, likely due to an early deficiency in somite segmentation (7,(9)(10)(11)(41)(42)(43)(44)(45)(46)(47). Nonetheless, double-mutant mice, wherein Prx1-Cre-mediated deletion of Psen1 is restricted to the mesenchyme on a Psen2 −/− background, survive for up to 10 wk and display radiodense bones (13).…”

Abnormal vertebral segmentation and the notch signaling pathway in man

“…The diseases that result from mutations in Notch signaling genes are surprisingly diverse, the affected organ systems including the vascular and central nervous systems; the skeleton, face, and limb; hematopoiesis; the determination of laterality; and the liver, heart, kidney and eye. Notch pathway genes and their associated diseases appear in Table 2 and several good review articles are available (Joutel and Tournier-Lasserve, 1998;Gridley, 1997Gridley, , 2003Gridley, , 2006Pourquié and Kusumi, 2001;Harper et al, 2003). As this review deals primarily with abnormalities of somitogenesis affecting the axial skeleton, consideration is now given to the DLL3, MESP2, LNFG, JAGGED1, and NOTCH2 genes.…”

Role and Function of Wnts in the Regulation of Myogenesis: When Wnt Meets Myostatin

“…These segmental masses correspond to a series of transient repeated epithelial structures that derive from the paraxial mesoderm and lie on either side of the neural tube [128]. Somites eventually differentiate into five major cell types: cartilage, bone, and tendons of the trunk, skeletal muscles of the body and the dermis of the back [128,129,130,131]. This process is regulated by sonic hedgehog (Shh) and Wnt signals that are secreted by tissues surrounding the somites [132,133].…”