Hox genes and mammalian development

We have examined the interactions of Hox genes in forming a cervical vertebrae, hindbrain, and limbs. In each case, it is apparent that individual Hox genes are performing individual functions but that more profound roles are apparent when they act in combination with others Hox genes. The observed interactions suggest that multiple Hox genes function in concert to regulate overlapping sets of target genes. This suggesting is particularly strong in the interactions observed among the group-3 analogous genes in formation of the cervical vertebrae and among Hoxd11, Hoxd12, and Hoxd13 in formation of the autopod. In each case, the cumulative effect of combining multiple mutations is the deletions of structure, resulting from either lack of specification or lack of specification or lack of proliferation of the precursor cells needed to from the structures. Similarly, the combination of HoxaI and HoxbI mutations results in more extensive deletions of anterior structures than is apparent in mice homozygous for either individual mutation. All the results, both of single and combined mutations, are compatible with a role of Hox genes in the early regionalization of the embryo. In the absence of Hox gene functions, formation of the axes and germ cell layers of the embryo still occurs. At this point, the Hox genes are activated to initiate the formation of the embryo by conferring positional value along the major axes of the embryo. Perhaps the most primitive function of Hox genes is the innate ability, through their chromosomal organization, to covet a series of temporal signals into morphological direction, a conversion of time's arrow into a spatial vector.