HOMEOBOX GENES AND THE MOLECULAR CONTROL OF LIMB PATTERN

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DESCRIPTION: This proposal represents a global characterization of the expression of HOX genes during the development of the limb. Tabin argues that expression of specific hox genes controls stage and region specific cell proliferation in the limb bud. Previous work from the Tabin laboratory has shown that these genes are expressed in a nested patterns along the proximal distal and anterior posterior axis of the limb bud. In preliminary experiments, Tabin describes the isolation and expression of an almost complete set of these genes in chick. In the current application, Tabin proposes to compare the phenotypic consequences of misexpressing individual HOX in the limb and to alter the times of misexpression to determine whether these genes affect proliferation of the undifferentiated cell mass or growth of established skeletal elements. Phenotypic consequences will be assayed both morphologically and in terms of cell proliferation to identify the specific cells affected. In a second project Tabin will use differential display to identify downstream targets of HOX gene expression. These targets will be used to examine the specificity of HOX genes for there specific targets.