Hindlimb patterning and mandible development require the Ptx1 gene

The restricted expression of the Ptx1 (Pitx1) gene in the posterior half of the lateral plate mesoderm has suggested that it may play a role in specif ication of posterior structures, in particular, specification of hindlimb i dentity, Ptx1 is also expressed in the most anterior ectoderm, the stomodeu m, and in the first branchial arch. Ptx1 expression overlaps with that of P tx2 in stomodeum and in posterior left lateral plate mesoderm, We now show that targeted inactivation of the mouse Ptx1 gene severely impairs hindlimb development: the ilium and knee cartilage are absent and the long bones ar e underdeveloped. Greater reduction of the right femur size in Ptx1 null mi ce suggests partial compensation by Ptx2 on the left side. The similarly si zed tibia and fibula of mutant hindlimbs may be taken to resemble forelimb bones: however, the mutant limb buds appear to have retained their molecula r identity as assessed by forelimb expression of Tbx5 and by hindlimb expre ssion of Tbx1, even though Tbx1 expression is decreased in Ptx1 null mice, The hindlimb defects appear to be, at least partly, due to abnormal chondro genesis. Since the most affected structures derive from the dorsal side of hindlimb buds, the data suggest that Ptx1 is responsible for patterning of these dorsal structures and that as such it may control development of hind limb-specific features. Ptx1 inactivation also leads to loss of bones deriv ed from the proximal part of the mandibular mesenchyme. The dual role of Pt x1 revealed by the gene knockout may reflect features of the mammalian jaw and hindlimbs that were acquired at a similar time during tetrapod evolutio n.