THE MOUSE ENGRAILED-1 GENE AND VENTRAL LIMB PATTERNING

DURING vertebrate limb development, positional information must be spe cified along three distinct axes. Although much progress has been made in our understanding of the molecular interactions involved in anteri or-posterior and proximal-distal limb patterning, less is known about dorsal-ventral patterning(1-3). The genes Wnt-7a and Lmx-1,which are e xpressed in dorsal limb ectoderm and mesoderm, respectively, are thoug ht to be important regulators of dorsal limb differentiation(4-6). Whe ther a complementary set of molecules controls ventral limb developmen t has not been clear. Here we report that Engrailed-1, a homeodamain-c ontaining transcription factor expressed in embryonic central limb ect oderm(7,8), is essential for ventral limb patterning. Loss of Engraile d-1 function in mice results in dorsal transformations of ventral paw structures, and in subtle alterations along the proximal-distal limb a ds. Engrailed-1 seems to act in part by repressing dorsal differentiat ion induced by Wnt-7a, and is essential for proper formation of the ap ical ectodermal ridge.