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 specification of posterior structures, in particular, specification of hindlimb identity. Ptx1 is also expressed in the most anterior ectoderm, the stomodeum, and in the first branchial arch. Ptx1 expression overlaps with that of Ptx2 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 are underdeveloped. Greater reduction of the right femur size in Ptx1 null mice suggests partial compensation by Ptx2 on the left side. The similarly sized tibia and fibula of mutant hindlimbs may be taken to resemble forelimb bones: however, the mutant limb buds appear to have retained their molecular identity as assessed by forelimb expression of Tbx5 and by hindlimb expression of Tbx4, even though Tbx4 expression is decreased in Ptx1 null mice. The hindlimb defects appear to be, at least partly, due to abnormal chondrogenesis. 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 hindlimb-specific features. Ptx1 inactivation also leads to loss of bones derived from the proximal part of the mandibular mesenchyme. The dual role of Ptx1 revealed by the gene knockout may reflect features of the mammalian jaw and hindlimbs that were acquired at a similar time during tetrapod evolution.
Lanctôt
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C
Laboratoire de génétique moléculaire, Institut de recherches cliniques de Montréal, Montréal Québec, Canada H2W 1R7.
Moreau
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A
Chamberland
M
M
Tremblay
M L
ML
Drouin
J
J
D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning; D001842:Bone and Bones / Q000196:embryology; D005314:Embryonic and Fetal Development; D005552:Forelimb / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D006614:Hindlimb / Q000196:embryology; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D008334:Mandible / Q000196:embryology*; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins; D010012:Osteogenesis; D051761:Paired Box Transcription Factors; D015183:Restriction Mapping; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D000097577:Homeobox Protein PITX2
D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C101485:homeobox protein PITX1