Nature 358, 236 - 239 (16 July 1992); doi:10.1038/358236a0

Targeted misexpression of Hox-4.6 in the avian limb bud causes apparent homeotic transformations

Bruce A. Morgan^*, Juan -Carlos Izpisúa-Belmonte^†‡, Denis Duboule^† & Clifford J. Tabin^*

^*Department of Genetics, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA
^†European Molecular Biology Laboratory, 6900 Heidelberg, Germany
^‡Present address: Department of Biological Chemistry, University of California, Los Angeles, California 90024-1737, USA

IN the limb bud the 5' members of the Hox-4 gene cluster are expressed in a nested set of overlapping domains which are progressively restricted in the posterior and distal directions¹. These domains arise early in limb bud development and come to approximate the primordia of the major structural elements of the limb along the anterior/posterior axis² (Fig. 1). This pattern, and the fact that surgical manipulations which lead to mirror image duplications along the anterior/posterior axis give rise to mirror image duplications of the domains of expression of these genes, have led to the proposal that these transcription factors specify positional identity along the anterior/posterior axis^3,4. Here we test this hypothesis directly using replication-competent retroviral vectors to expand the domain of expression of the Hox-4.6 gene anteriorly during limb development in vivo.We report that alteration of the domain of expression of the Hox-4.6 gene in the developing limb leads to reproducible pattern alterations consistent with a posterior homeotic transformation.

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