INDUCTION OF THE LIM HOMEOBOX GENE LMX1 BY WNT7A ESTABLISHES DORSOVENTRAL PATTERN IN THE VERTEBRATE LIMB

During vertebrate limb development, the ectoderm directs the dorsovent ral patterning of the underlying mesoderm. To define the molecular eve nts involved in this process, we have analyzed the function of WNT7a, a secreted factor expressed in the dorsal ectoderm, and LMX1, a LIM ho meodomain transcription factor expressed in the dorsal mesenchyme. Ect opic expression of Wnt7a is sufficient to induce and maintain Lmx1 exp ression in limb mesenchyme, both in vivo and in vitro. Ectopic express ion of Lmx1 in the ventral mesenchyme is sufficient to generate double -dorsal limbs. Thus, the dorsalization of limb mesoderm appears to inv olve the WNT7a-mediated induction of Lmx1 in limb mesenchymal cells.