QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

doi: 10.1242/10.1242/dev.00367

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by White, P. H. Articles by Chapman, D. L. Search for Related Content PubMed PubMed Citation Articles by White, P. H. Articles by Chapman, D. L.

Defective somite patterning in mouse embryos with reduced levels of Tbx6

Phillip H. White, Deborah R. Farkas, Erin E. McFadden^* and Deborah L. Chapman

Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
^* Present address: UC Davis School of Veterinary Medicine, Davis, CA 95616, USA

Author for correspondence (e-mail: dlc7{at}pitt.edu)

Accepted 20 December 2002

During vertebrate embryogenesis, paraxial mesoderm gives rise to somites, which subsequently develop into the dermis, skeletal muscle, ribs and vertebrae of the adult. Mutations that disrupt the patterning of individual somites have dramatic effects on these tissues, including fusions of the ribs and vertebrae. The T-box transcription factor, Tbx6, is expressed in the paraxial mesoderm but is downregulated as somites develop. It is essential for the formation of posterior somites, which are replaced with ectopic neural tubes in Tbx6-null mutant embryos. We show that partial restoration of Tbx6 expression in null mutants rescues somite development, but that rostrocaudal patterning within them is defective, ultimately resulting in rib and vertebral fusions, demonstrating that Tbx6 activity in the paraxial mesoderm is required not simply for somite specification but also for their normal patterning. Somite patterning is dependent upon Notch signaling and we show that Tbx6 genetically interacts with the Notch ligand, delta-like 1 (Dll1). Dll1 expression, which is absent in the Tbx6-null mutant, is restored at reduced levels in the partially rescued mutants, suggesting that Dll1 is a target of Tbx6. We also identify the spontaneous mutation rib-vertebrae as a hypomorphic mutation in Tbx6. The similarity in the phenotypes we describe here and that of some human birth defects, such as spondylocostal dysostosis, raises the possibility that mutations in Tbx6 or components of this pathway may be responsible for these defects.

Key words: Mouse, Somitogenesis, Segmentation, T-box, Tbx6, Dll1, rib-vertebrae

Related articles in Development:

Notching up somite patterning roles for Tbx6

Development 2003 130: 805. [Full Text]  

This article has been cited by other articles:

				I. Rubio-Aliaga, D. Soewarto, S. Wagner, M. Klaften, H. Fuchs, S. Kalaydjiev, D. H. Busch, M. Klempt, B. Rathkolb, E. Wolf, et al. A Genetic Screen for Modifiers of the Delta1-Dependent Notch Signaling Function in the Mouse Genetics, March 1, 2007; 175(3): 1451 - 1463. [Abstract] [Full Text] [PDF]

				Y. Yasuhiko, S. Haraguchi, S. Kitajima, Y. Takahashi, J. Kanno, and Y. Saga Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression PNAS, March 7, 2006; 103(10): 3651 - 3656. [Abstract] [Full Text] [PDF]

				S. Shi, M. Stahl, L. Lu, and P. Stanley Canonical Notch Signaling Is Dispensable for Early Cell Fate Specifications in Mammals Mol. Cell. Biol., November 1, 2005; 25(21): 9503 - 9508. [Abstract] [Full Text] [PDF]

				B. Davidson, W. Shi, and M. Levine Uncoupling heart cell specification and migration in the simple chordate Ciona intestinalis Development, November 1, 2005; 132(21): 4811 - 4818. [Abstract] [Full Text] [PDF]

				K. Good, R. Ciosk, J. Nance, A. Neves, R. J. Hill, and J. R. Priess The T-box transcription factors TBX-37 and TBX-38 link GLP-1/Notch signaling to mesoderm induction in C. elegans embryos Development, May 1, 2004; 131(9): 1967 - 1978. [Abstract] [Full Text] [PDF]