HOX9 GENES AND VERTEBRATE LIMB SPECIFICATION

Development of paired appendages at appropriate levels along the prima ry body axis is a hallmark of the body plan of jawed vertebrates. Hox genes are good candidates for encoding position in lateral plate mesod erm along the body axis(1,2) and thus for determining where limbs are formed. Local application of fibroblast growth factors (FGFs) to the a nterior prospective flank of a chick embryo induces development of an ectopic wing, and FGF applied to posterior flank induces an ectopic le g(3). If particular combinations of Hox gene expression determine wher e wings and legs develop, then formation of additional limbs from flan k should involve changes in Hox gene expression that reflect the type of limb induced. Here we show that the same population of flank cells can be induced to form either a wing or a leg, and that induction of t hese ectopic limbs is accompanied by specific changes in expression of three Hox genes in lateral plate mesoderm. This then reproduces, in t he flank, expression patterns found at normal Limb levels. Hox gene ex pression is reprogrammed in lateral plate mesoderm, but is unaffected in paraxial mesoderm. Independent regulation of Hox gene expression in lateral plate mesoderm may have been a key step in the evolution of p aired appendages.