Closely related homeobox proteins, MOX-1 and MOX-2, belong to a family of nonclustered, diverged homeobox genes that are expressed in overlapping patterns in the paraxial mesoderm and its derivatives. MOX-1 and MOX-2 function transiently in the formation of mesodermal and mesenchymal derivatives. MOX-1 and MOX-2 are implicated in the early steps of mesoderm formation during gastrulation. In addition, the MOX proteins are also involved in somatic differentiation. Significantly, MOX-1 associates more strongly with Pax1, whereas MOX-2 preferentially associates with Pax3. Specifically, expression of MOX-2, also known as Mesenchyme homeobox 2 and GAX, has been shown to be critical in axial skeleton development. MOX-2 is not needed for the migration of myogenic precursors into the limb bud, but it is essential for normal appendicular muscle formation and for the normal regulation of myogenic genes. MOX-2 is expressed in placental tissue. The human MEOX2 gene maps to chromosome 7p22.1-p21.3 and encodes the MOX-2 protein. Mutations in the gene may be involved in craniofacial and/or skeletal abnormalities.