Evidence for a Myotomal Hox/Myf Cascade Governing Nonautonomous Control of Rib Specification within Global Vertebral Domains

SummaryHox 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.

Graphical AbstractFigure optionsDownload high-quality image (359 K)Download as PowerPoint slideHighlights
► Hox group 6 genes are able to induce ribs
► Hox group 6 and 10 proteins regulate Myf5/Myf6 expression in the hypaxial myotome
► Myf5 and Myf6 have a redundant nonmyogenic role in rib development
► Myf5/Myf6 convey information to the sclerotome using a cell nonautonomous mechanism