Evidence for a myotomal Hox/Myf cascade governing nonautonomous control of rib specification within global vertebral domains.
Hox genes are essential for the patterning of the axial skeleton. Hox group 10 has been shown to specify the lumbar domain by setting a rib-inhibiting program in the presomitic mesoderm (PSM). We have now produced mice with ribs in every vertebra by ectopically expressing Hox group 6 in the PSM, indicating that Hox genes are also able to specify the thoracic domain. We show that the information provided by Hox genes to specify rib-containing and rib-less areas is first interpreted in the myotome through the regional-specific control of Myf5 and Myf6 expression. This information is then transmitted to the sclerotome by a system that includes FGF and PDGF signaling to produce vertebrae with or without ribs at different axial levels. Our findings offer a new perspective of how Hox genes produce global patterns in the axial skeleton and support a redundant nonmyogenic role of Myf5 and Myf6 in rib formation.
Vinagre
Tânia
T
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal.
Moncaut
Natalia
N
Carapuço
Marta
M
Nóvoa
Ana
A
Bom
Joana
J
Mallo
Moisés
M
D000818:Animals; D001846:Bone Development; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D008957:Models, Genetic; D024510:Muscle Development; D051787:Myogenic Regulatory Factor 5 / Q000502:physiology*; D018006:Myogenic Regulatory Factors / Q000502:physiology*; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000378:metabolism
D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D010982:Platelet-Derived Growth Factor; C063403:myogenic factor 6; C092119:Hoxa10 protein, mouse; D005346:Fibroblast Growth Factors