|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 23 March 2005
doi: 10.1242/dev.01773
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Département Génétique, Développement et Pathologie
Moléculaire, Institut Cochin – INSERM 567, CNRS UMR 8104,
Université Paris V, 24 Rue du Faubourg Saint Jacques 75014 Paris,
France
2 Plateforme de recombinaison homologue, Institut Cochin – INSERM 567,
CNRS UMR 8104, Université Paris V, 24 Rue du Faubourg Saint Jacques
75014 Paris, France
3 Plateforme d'histologie, Institut Cochin – INSERM 567, CNRS UMR 8104,
Université Paris V, 24 Rue du Faubourg Saint Jacques 75014 Paris,
France
4 Division of Medical and Molecular Genetics, Guy's Hospital, London SE1 9RT,
UK
Author for correspondence (e-mail:
maire{at}cochin.inserm.fr)
Accepted 9 February 2005
In mammals, Six5, Six4 and Six1 genes are co-expressed during mouse myogenesis. Six4 and Six5 single knockout (KO) mice have no developmental defects, while Six1 KO mice die at birth and show multiple organ developmental defects. We have generated Six1Six4 double KO mice and show an aggravation of the phenotype previously reported for the single Six1 KO. Six1Six4 double KO mice are characterized by severe craniofacial and rib defects, and general muscle hypoplasia. At the limb bud level, Six1 and Six4 homeogenes control early steps of myogenic cell delamination and migration from the somite through the control of Pax3 gene expression. Impaired in their migratory pathway, cells of the somitic ventrolateral dermomyotome are rerouted, lose their identity and die by apoptosis. At the interlimb level, epaxial Met expression is abolished, while it is preserved in Pax3-deficient embryos. Within the myotome, absence of Six1 and Six4 impairs the expression of the myogenic regulatory factors myogenin and Myod1, and Mrf4 expression becomes undetectable. Myf5 expression is correctly initiated but becomes restricted to the caudal region of each somite. Early syndetomal expression of scleraxis is reduced in the Six1Six4 embryo, while the myotomal expression of Fgfr4 and Fgf8 but not Fgf4 and Fgf6 is maintained. These results highlight the different roles played by Six proteins during skeletal myogenesis.
Key words: Six/sine oculis homeoproteins, Pax3, Myogenesis, Hypaxial lip, Migration, Myotome, Syndetome
Related articles in Development:
This article has been cited by other articles:
|
|
 |
|
  E. Kutejova, B. Engist, M. Self, G. Oliver, P. Kirilenko, and N. Bobola Six2 functions redundantly immediately downstream of Hoxa2 Development, April 15, 2008; 135(8): 1463 - 1470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Coletta, K. L. Christensen, D. S. Micalizzi, P. Jedlicka, M. Varella-Garcia, and H. L. Ford Six1 Overexpression in Mammary Cells Induces Genomic Instability and Is Sufficient for Malignant Transformation Cancer Res., April 1, 2008; 68(7): 2204 - 2213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Schlosser How old genes make a new head: redeployment of Six and Eya genes during the evolution of vertebrate cranial placodes Integr. Comp. Biol., September 1, 2007; 47(3): 343 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Giordani, L. Bajard, J. Demignon, P. Daubas, M. Buckingham, and P. Maire Six proteins regulate the activation of Myf5 expression in embryonic mouse limbs PNAS, July 3, 2007; 104(27): 11310 - 11315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhu, A. S. Gleiberman, and M. G. Rosenfeld Molecular Physiology of Pituitary Development: Signaling and Transcriptional Networks Physiol Rev, July 1, 2007; 87(3): 933 - 963. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yu, E. Davicioni, T. J. Triche, and G. Merlino The Homeoprotein Six1 Transcriptionally Activates Multiple Protumorigenic Genes but Requires Ezrin to Promote Metastasis Cancer Res., February 15, 2006; 66(4): 1982 - 1989. [Abstract] [Full Text] [PDF]
|
|
