THE EXPRESSION PATTERN OF THE DISTAL-LESS HOMEOBOX-CONTAINING GENE DLX-5 IN THE DEVELOPING CHICK LIMB BUD SUGGESTS ITS INVOLVEMENT IN APICAL ECTODERMAL RIDGE ACTIVITY, PATTERN-FORMATION, AND CARTILAGE DIFFERENTIATION

Here we report the isolation from a chick limb bud cDNA library of a c DNA that contains the full coding sequence of chicken Dlx-5, a member of the Distal-less (Dlx) family of homeobox-containing genes that enco de homeodomains highly similar to that of the Drosophila Distal-less g ene, a gene that is required for limb development in the Drosophila em bryo. The expression pattern of Dlx-5 in the developing chick limb bud suggests that it may be involved in several aspects of limb morphogen esis. Dlx-5 is expressed in the apical ectodermal ridge (AER) which di rects the outgrowth and patterning of underlying limb mesoderm. During early limb development Dlx-5 is also expressed in the mesoderm at the anterior margin of the limb bud and in a discrete group of mesodermal cells at the mid-proximal posterior margin that corresponds to the po sterior necrotic zone. These mesodermal domains of Dlx-5 expression ro ughly correspond to the anterior and posterior boundaries of the progr ess zone, the group of highly proliferating undifferentiated mesoderma l cells underneath the AER that will give rise to the skeletal element s of the limb and associated structures. The AER and anterior and post erior mesodermal domains of Dlx-5 expression are regions in which the homeobox-containing gene Msx-2 is also highly expressed, suggesting th at Dlx-5 and Msx-2 might be involved in regulatory networks that contr ol AER activity and demarcate the progress zone. In addition, Dlx-5 is expressed in high amounts by the differentiating cartilaginous skelet al elements of the limb, suggesting it may be involved in regulating t he onset of limb cartilage differentiation.