|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online November 3, 2003
doi: 10.1242/10.1242/dev.00793
1 Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive
Cancer Center and Hospital, Keck School of Medicine, University of Southern
California, 1441 Eastlake Avenue, Los Angeles, CA 90089-9176, USA
2 Department of Morphology, Faculty of Medicine, Ben Gurion University of the
Negev, Beer Sheva, Israel
3 Department of Craniofacial Development, King's College, London, UK
4 Institute for Genetic Medicine, Keck School of Medicine, University of
Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089-9176,
USA
* Author for correspondence (e-mail: maxson{at}hsc.usc.edu)
Accepted 11 August 2003
The flat bones of the vertebrate skull vault develop from two migratory mesenchymal cell populations, the cranial neural crest and paraxial mesoderm. At the onset of skull vault development, these mesenchymal cells emigrate from their sites of origin to positions between the ectoderm and the developing cerebral hemispheres. There they combine, proliferate and differentiate along an osteogenic pathway. Anomalies in skull vault development are relatively common in humans. One such anomaly is familial calvarial foramina, persistent unossified areas within the skull vault. Mutations in MSX2 and TWIST are known to cause calvarial foramina in humans. Little is known of the cellular and developmental processes underlying this defect. Neither is it known whether MSX2 and TWIST function in the same or distinct pathways. We trace the origin of the calvarial foramen defect in Msx2 mutant mice to a group of skeletogenic mesenchyme cells that compose the frontal bone rudiment. We show that this cell population is reduced not because of apoptosis or deficient migration of neural crest-derived precursor cells, but because of defects in its differentiation and proliferation. We demonstrate, in addition, that heterozygous loss of Twist function causes a foramen in the skull vault similar to that caused by loss of Msx2 function. Both the quantity and proliferation of the frontal bone skeletogenic mesenchyme are reduced in Msx2-Twist double mutants compared with individual mutants. Thus Msx2 and Twist cooperate in the control of the differentiation and proliferation of skeletogenic mesenchyme. Molecular epistasis analysis suggests that Msx2 and Twist do not act in tandem to control osteoblast differentiation, but function at the same epistatic level.
Key words: Skull vault, Calvarial foramina, Msx2, Twist, Neural crest, Mouse
Related articles in Development:
This article has been cited by other articles:
|
|
 |
|
  H.-F. Yuen, W.-K. Kwok, K.-K. Chan, C.-W. Chua, Y.-P. Chan, Y.-Y. Chu, Y.-C. Wong, X. Wang, and K.-W. Chan TWIST modulates prostate cancer cell-mediated bone cell activity and is upregulated by osteogenic induction Carcinogenesis, August 1, 2008; 29(8): 1509 - 1518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Merrill, B. F. Eames, S. J. Weston, T. Heath, and R. A. Schneider Mesenchyme-dependent BMP signaling directs the timing of mandibular osteogenesis Development, April 1, 2008; 135(7): 1223 - 1234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Satoh, S. Hamada, K. Kimura, A. Kanno, M. Hirota, J. Umino, W. Fujibuchi, A. Masamune, N. Tanaka, K. Miura, et al. Up-Regulation of MSX2 Enhances the Malignant Phenotype and Is Associated with Twist 1 Expression in Human Pancreatic Cancer Cells Am. J. Pathol., April 1, 2008; 172(4): 926 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Spagnoli, L. O'Rear, R. L. Chandler, F. Granero-Molto, D. P. Mortlock, A. E. Gorska, J. A. Weis, L. Longobardi, A. Chytil, K. Shimer, et al. TGF-{beta} signaling is essential for joint morphogenesis J. Cell Biol., July 30, 2007; 177(6): 1105 - 1117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. F. Hu, Z.-J. Zhang, and M. Sieber-Blum An Epidermal Neural Crest Stem Cell (EPI-NCSC) Molecular Signature Stem Cells, December 1, 2006; 24(12): 2692 - 2702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Diamond, M. Amen, Q. Hu, H. M. Espinoza, and B. A. Amendt Functional interactions between Dlx2 and lymphoid enhancer factor regulate Msx2 Nucleic Acids Res., November 6, 2006; 34(20): 5951 - 5965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Khare, A. H. Taylor, J. C. Konje, and S. C. Bell {Delta}9-Tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription Mol. Hum. Reprod., May 1, 2006; 12(5): 321 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Merrill, E. G. Bochukova, S. M. Brugger, M. Ishii, D. T. Pilz, S. A. Wall, K. M. Lyons, A. O.M. Wilkie, and R. E. Maxson Jr Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis Hum. Mol. Genet., April 15, 2006; 15(8): 1319 - 1328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I. Reinhold, R. M. Kapadia, Z. Liao, and M. C. Naski The Wnt-inducible Transcription Factor Twist1 Inhibits Chondrogenesis J. Biol. Chem., January 20, 2006; 281(3): 1381 - 1388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Deckelbaum, A. Majithia, T. Booker, J. E. Henderson, and C. A. Loomis The homeoprotein engrailed 1 has pleiotropic functions in calvarial intramembranous bone formation and remodeling Development, January 1, 2006; 133(1): 63 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ishii, J. Han, H.-Y. Yen, H. M. Sucov, Y. Chai, and R. E. Maxson Jr Combined deficiencies of Msx1 and Msx2 cause impaired patterning and survival of the cranial neural crest Development, November 15, 2005; 132(22): 4937 - 4950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Gagliardi, E. Y. W. Kuo, S. Raulic, G. F. Wagner, and G. E. DiMattia Human stanniocalcin-2 exhibits potent growth-suppressive properties in transgenic mice independently of growth hormone and IGFs Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E92 - E105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Q. Hassan, A. Javed, M. I. Morasso, J. Karlin, M. Montecino, A. J. van Wijnen, G. S. Stein, J. L. Stein, and J. B. Lian Dlx3 Transcriptional Regulation of Osteoblast Differentiation: Temporal Recruitment of Msx2, Dlx3, and Dlx5 Homeodomain Proteins to Chromatin of the Osteocalcin Gene Mol. Cell. Biol., October 15, 2004; 24(20): 9248 - 9261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Brugger, A. E. Merrill, J. Torres-Vazquez, N. Wu, M.-C. Ting, J. Y.-M. Cho, S. L. Dobias, S. E. Yi, K. Lyons, J. R. Bell, et al. A phylogenetically conserved cis-regulatory module in the Msx2 promoter is sufficient for BMP-dependent transcription in murine and Drosophila embryos Development, October 15, 2004; 131(20): 5153 - 5165. [Abstract] [Full Text] [PDF]
|
|
