Mutation of the fucose-specific β1,3 N-acetylglucosaminyltransferase UNG results in abnormal formation of the spine (Reprinted)

Notch signaling is an evolutionarily conserved mechanism that determines cell fate in a variety of contexts during development. This is achieved through different modes of action that are context dependent. One mode involves boundary formation between two groups of cells. With this mode of action, Notch signaling is central to vertebrate evolution as it drives the segmentation of paraxial mesoderm in the formation of somites, which are the precursors of the vertebra. In this case, boundary formation facilitates a mesenchymal to epithelial transition, leading to the creation of a somite. In addition, the boundary establishes a signaling center that patterns the somite. a feature that directly impacts on vertebral column formation. Studies in Xenopus, zebrafish, chicken and mouse have established the importance of Notch signaling in somitogenesis, and indeed in mouse how perturbations in somitogenesis affect vertebral column formation. Spondylocostal dysostosis is a congenital disorder characterized by formation of abnormal vertebrae. Here, mutation in Notch pathway genes demonstrates that Notch signaling is also required for normal somite formation and vertebral column development in humans; of particular interest here is mutation of the LUNATIC FRINGE (LFNG) gene, which causes SCD type 3. LUNATIC FRINGE encodes for a fucose-specific PI,3-N-acetylglucosaminyltransferase, which modifies Notch receptors and alters Notch signaling activity. This review will focus on Notch glycolsylation, and the role of LUNATIC FRINGE in somite formation and vertebral column development in mice and humans. (C) 2008 Elsevier B.V. All rights reserved.