CONTRIBUTIONS OF THE 3' HOX GENES, HOXA1, HOXB1, AND HOXB2, TO PATTERNING OF THE AXIAL SKELETON DURING DEVELOPMENT

To investigate whether Hoxb1, as well as related proteins Hoxa1 and Hoxb2, are involved in vertebral development, we analyzed the skeletons of 18.5dpc Hoxa1, Hoxb1, and Hoxb2 loss-of-function single and double mutant embryos. Our analysis reveals that loss of Hoxb1 and Hoxb2 function leads to multiple homeotic transformations along the vertebral column. The dosages of both HoxB genes seem to be important, since the homeotic transformations significantly increase in penetrance in Hoxb1/Hoxb2 trans-heterozygotes, compared to single heterozygotes. Through the use of transgenic mouse strains, we were also able to reproduce similar transformations upon addition of extra HoxB gene copies. Interestingly, the defects observed in these loss-of-function mutants and transgenic mice occur at the boundaries between morphologically distinct vertebral domains. In conclusion, these data show that the anterior HoxB genes, particularly, Hoxb1 and Hoxb2, play a critical role in patterning the paraxial mesoderm that will give rise to the axial skeleton