Position-dependent expression of two related homeobox genes in developing vertebrate limbs

Many genes that control pattern formation in insects contain a conserved homeobox region which encodes a domain involved in DNA binding. One approach to understanding pattern formation in vertebrates is to examine the role of homeobox-containing genes in the developing limb. Two such genes, Hox-7.1 and Hox-8.1, are expressed in distal mesoderm, but not in the proximal core, of mouse forelimb (refs 3, 4, and D.R.D., manuscript in preparation). The proximodistal cartilage pattern in the chick wing is progressively determined in the distal mesoderm, which is maintained as a 'progress zone' by the overlying apical ectodermal ridge. Indeed, proximal cells are reprogrammed to form distal structures when placed in the progress zone and we therefore expect that genes involved in controlling limb pattern should be activated in such grafts. We tested this requirement for Hox-7.1 and Hox-8.1 in mouse limb mesoderm placed in chick wing buds. Our results reported here indicate that both genes are rapidly activated by a signal from the apical ectoderm. These properties, taken with the DNA-binding properties of the homeodomain, strongly suggest that Hox-7.1 and Hox-8.1 have fundamental roles in limb-pattern formation.