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Abstract. Homeobox-containing (HOX) genes are thought to be involved in the regulation of pattern formation and specification of positional information during vertebrate limb development. We report the isolation from a chick limb bud cDNA library of several overlapping chicken HOX cDNAs, which on the basis of their nucleotide and deduced amino acid sequences have been identified as corresponding to the chicken cognate of mouse Hox-7.1. The gene encoding these chicken (Gallus) HOX cDNAs has been designated GHox-7, and is a member of a family of vertebrate HOX genes that are highly similar in sequence to the Drosophila msh gene. GHox-7 encodes an mRNA transcript of about 1.8–2.0 kb that is expressed at early stages of chick limb development. In situ hybridization analysis has revealed that GHox-7 is expressed in limb bud mesoderm in a temporal and spatial fashion. This is consistent with its involvement in specifying anterior positional identity and/or in the response of limb mesenchymal cells to the apical ectodermal ridge (AER), which directs polarized proximodistal limb outgrowth. At early stages (stages 20–21) of chick limb development when positional values along the anterior-posterior (A-P) axis are being specified, GHox-7 exhibits an asymmetric arc of expression extending from the anterior border of the limb bud to the mesenchymal cells directly subjacent to the AER. The graded expression domain of GHox-7 does not extend into the extreme posterior border of the limb bud that contains the zone of polarizing activity (ZPA) which is thought to be the source of a morphogen that is involved in the specification of positional identities along the A-P axis. At later stages of development (stages 23–25), GHox-7 is expressed in high amounts in the proximal anterior periphery of the wing bud, with no detectable expression in the proximal dorsal and ventral (myogenic) regions, or in the chondrogenic central core. In this posterior periphery of the wing bud at these later stages of development, expression of GHox-7 is limited to a small region in the mid-proximal periphery corresponding to the posterior necrotic zone in which programmed cell death is occurring. The possible involvement of GHox-7 in programmed cell death during limb development is also suggested by the fact that it is expressed in the necrotic interdigital mesenchyme in 6–7 day (stage 31–32) wing buds.