Oscillatory lunatic fringe activity is crucial for segmentation of the anterior but not posterior skeleton
Author:
Shifley Emily T.1, VanHorn Kellie M.1, Perez-Balaguer Ariadna1, Franklin John D.1, Weinstein Michael1, Cole Susan E.1
Affiliation:
1. Department of Molecular Genetics, The Ohio State University, 984 Biological Sciences Building, 484 West 12th Avenue, Columbus, OH 43210-1292,USA.
Abstract
The Notch pathway plays multiple roles during vertebrate somitogenesis,functioning in the segmentation clock and during rostral/caudal (R/C) somite patterning. Lunatic fringe (Lfng) encodes a glycosyltransferase that modulates Notch signaling, and its expression patterns suggest roles in both of these processes. To dissect the roles played by Lfng during somitogenesis, a novel allele was established that lacks cyclic Lfngexpression within the segmentation clock, but that maintains expression during R/C somite patterning (LfngΔFCE1). In the absence of oscillatory Lfng expression, Notch activation is ubiquitous in the PSM of LfngΔFCE1 embryos. LfngΔFCE1 mice exhibit severe segmentation phenotypes in the thoracic and lumbar skeleton. However, the sacral and tail vertebrae are only minimally affected in LfngΔFCE1mice, suggesting that oscillatory Lfng expression and cyclic Notch activation are important in the segmentation of the thoracic and lumbar axial skeleton (primary body formation), but are largely dispensable for the development of sacral and tail vertebrae (secondary body formation). Furthermore, we find that the loss of cyclic Lfng has distinct effects on the expression of other clock genes during these two stages of development. Finally, we find that LfngΔFCE1 embryos undergo relatively normal R/C somite patterning, confirming that Lfngroles in the segmentation clock are distinct from its functions in somite patterning. These results suggest that the segmentation clock may employ varied regulatory mechanisms during distinct stages of anterior/posterior axis development, and uncover previously unappreciated connections between the segmentation clock, and the processes of primary and secondary body formation.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference55 articles.
1. Aulehla, A. and Johnson, R. L. (1999). Dynamic expression of lunatic fringe suggests a link between notch signaling and an autonomous cellular oscillator driving somite segmentation. Dev. Biol.207,49-61. 2. Aulehla, A., Wehrle, C., Brand-Saberi, B., Kemler, R., Gossler,A., Kanzler, B. and Herrmann, B. G. (2003). Wnt3a plays a major role in the segmentation clock controlling somitogenesis. Dev. Cell4,395-406. 3. Bulman, M. P., Kusumi, K., Frayling, T. M., McKeown, C.,Garrett, C., Lander, E. S., Krumlauf, R., Hattersley, A. T., Ellard, S. and Turnpenny, P. D. (2000). Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis. Nat. Genet.24,438-441. 4. Bunting, M., Bernstein, K. E., Greer, J. M., Capecchi, M. R. and Thomas, K. R. (1999). Targeting genes for self-excision in the germ line. Genes Dev.13,1524-1528. 5. Candia, A. F., Hu, J., Crosby, J., Lalley, P. A., Noden, D.,Nadeau, J. H. and Wright, C. V. (1992). Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. Development116,1123-1136.
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