Development, Vol 128, Issue 10 1911-1921, Copyright © 2001 by Company of Biologists

JOURNAL ARTICLES

Axial skeletal patterning in mice lacking all paralogous group 8 Hox genes

E van Den Akker, C Fromental-Ramain, W de Graaff, H Le Mouellic, P Brulet, P Chambon and J Deschamps
Hubrecht Laboratory, The Netherlands Institute for Developmental Biology, Uppsalalaan 8, Utrecht, The Netherlands. jacqueli@niob.knaw.nl

We present a detailed study of the genetic basis of mesodermal axial patterning by paralogous group 8 Hox genes in the mouse. The phenotype of Hoxd8 loss-of-function mutants is presented, and compared with that of Hoxb8- and Hoxc8-null mice. Our analysis of single mutants reveals common features for the Hoxc8 and Hoxd8 genes in patterning lower thoracic and lumbar vertebrae. In the Hoxb8 mutant, more anterior axial regions are affected. The three paralogous Hox genes are expressed up to similar rostral boundaries in the mesoderm, but at levels that strongly vary with the axial position. We find that the axial region affected in each of the single mutants mostly corresponds to the area with the highest level of gene expression. However, analysis of double and triple mutants reveals that lower expression of the other two paralogous genes also plays a patterning role when the mainly expressed gene is defective. We therefore conclude that paralogous group 8 Hox genes are involved in patterning quite an extensive anteroposterior (AP) axial region. Phenotypes of double and triple mutants reveal that Hoxb8, Hoxc8 and Hoxd8 have redundant functions at upper thoracic and sacral levels, including positioning of the hindlimbs. Interestingly, loss of functional Hoxb8 alleles partially rescues the phenotype of Hoxc8- and Hoxc8/Hoxd8-null mutants at lower thoracic and lumbar levels. This suggests that Hoxb8 affects patterning at these axial positions differently from the other paralogous gene products. We conclude that paralogous Hox genes can have a unique role in patterning specific axial regions in addition to their redundant function at other AP levels.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				K. Harada, T. Yamazaki, C. Iwata, Y. Yoshimatsu, H. Sase, K. Mishima, Y. Morishita, M. Hirashima, Y. Oike, T. Suda, et al. Identification of targets of Prox1 during in vitro vascular differentiation from embryonic stem cells: functional roles of HoxD8 in lymphangiogenesis J. Cell Sci., November 1, 2009; 122(21): 3923 - 3930. [Abstract] [Full Text] [PDF]

				J. B. Gross, M. Protas, M. Conrad, P. E. Scheid, O. Vidal, W. R. Jeffery, R. Borowsky, and C. J. Tabin Gene Networks in Development and Evolution Special Feature Sackler Colloquium: Synteny and candidate gene prediction using an anchored linkage map of Astyanax mexicanus PNAS, December 23, 2008; 105(51): 20106 - 20111. [Abstract] [Full Text] [PDF]

				S. J. Gaunt, D. Drage, and R. C. Trubshaw Increased Cdx protein dose effects upon axial patterning in transgenic lines of mice Development, August 1, 2008; 135(15): 2511 - 2520. [Abstract] [Full Text] [PDF]

				D. C. McIntyre, S. Rakshit, A. R. Yallowitz, L. Loken, L. Jeannotte, M. R. Capecchi, and D. M. Wellik Hox patterning of the vertebrate rib cage Development, August 15, 2007; 134(16): 2981 - 2989. [Abstract] [Full Text] [PDF]

				L. M. Helvering, R. Liu, N. H. Kulkarni, T. Wei, P. Chen, S. Huang, F. Lawrence, D. L. Halladay, R. R. Miles, E. M. Ambrose, et al. Expression Profiling of Rat Femur Revealed Suppression of Bone Formation Genes by Treatment with Alendronate and Estrogen but Not Raloxifene Mol. Pharmacol., November 1, 2005; 68(5): 1225 - 1238. [Abstract] [Full Text] [PDF]

				M. Carapuco, A. Novoa, N. Bobola, and M. Mallo Hox genes specify vertebral types in the presomitic mesoderm Genes & Dev., September 15, 2005; 19(18): 2116 - 2121. [Abstract] [Full Text] [PDF]

				C. L. McNulty, J. N. Peres, N. Bardine, W. M. R. van den Akker, and A. J. Durston Knockdown of the complete Hox paralogous group 1 leads to dramatic hindbrain and neural crest defects Development, June 15, 2005; 132(12): 2861 - 2871. [Abstract] [Full Text] [PDF]

				W. de Graaff, D. Tomotsune, T. Oosterveen, Y. Takihara, H. Koseki, and J. Deschamps Randomly inserted and targeted Hox/reporter fusions transcriptionally silenced in Polycomb mutants PNAS, November 11, 2003; 100(23): 13362 - 13367. [Abstract] [Full Text] [PDF]

				A. H. Juan and F. H. Ruddle Enhancer timing of Hox gene expression: deletion of the endogenous Hoxc8 early enhancer Development, October 15, 2003; 130(20): 4823 - 4834. [Abstract] [Full Text] [PDF]

				G. J. Miller, H. L. Miller, A. van Bokhoven, J. R. Lambert, P. N. Werahera, O. Schirripa, M. S. Lucia, and S. K. Nordeen Aberrant HOXC Expression Accompanies the Malignant Phenotype in Human Prostate Cancer Res., September 15, 2003; 63(18): 5879 - 5888. [Abstract] [Full Text] [PDF]

				M. Kmita and D. Duboule Organizing Axes in Time and Space; 25 Years of Colinear Tinkering Science, July 18, 2003; 301(5631): 331 - 333. [Abstract] [Full Text] [PDF]

				D. M. Wellik and M. R. Capecchi Hox10 and Hox11 Genes Are Required to Globally Pattern the Mammalian Skeleton Science, July 18, 2003; 301(5631): 363 - 367. [Abstract] [Full Text] [PDF]

				D. M. Wellik, P. J. Hawkes, and M. R. Capecchi Hox11 paralogous genes are essential for metanephric kidney induction Genes & Dev., June 1, 2002; 16(11): 1423 - 1432. [Abstract] [Full Text] [PDF]

				P. te Welscher, M. Fernandez-Teran, M. A. Ros, and R. Zeller Mutual genetic antagonism involving GLI3 and dHAND prepatterns the vertebrate limb bud mesenchyme prior to SHH signaling Genes & Dev., February 15, 2002; 16(4): 421 - 426. [Abstract] [Full Text] [PDF]

				E. van den Akker, S. Forlani, K. Chawengsaksophak, W. de Graaff, F. Beck, B. I. Meyer, and J. Deschamps Cdx1 and Cdx2 have overlapping functions in anteroposterior patterning and posterior axis elongation Development, January 5, 2002; 129(9): 2181 - 2193. [Abstract] [Full Text] [PDF]