Deletion of the Pitx1 genomic locus affects mandibular tooth morphogenesis and expression of the Barx1 and Tbx1 genes.
Pitx1 is a bicoid-related homeodomain factor that exhibits preferential expression in the developing hindlimb, mandible, pituitary gland and teeth. Pitx1 gene-deleted mice exhibit striking abnormalities in morphogenesis and growth of both hindlimb and mandible, suggesting a proliferative defect in these two structures. Here, we studied the expression and regulation of Pitx1 in both mandible and developing teeth and analyzed tooth morphology, cell proliferation, apoptosis and expression of Pitx2, Barx1 and Tbx1 in dental tissues of Pitx1-/- mouse embryos. Pitx1 expression is restricted to the epithelium of the growing tooth anlagen. Tissue recombination and bead implantation experiments demonstrated that bone morphogenetic protein-4 down-regulates Pitx1 expression in both mandibular mesenchyme and dental epithelium. Deletion of the Pitx1 locus results in micrognathia and abnormal morphology of the mandibular molars. Although Pitx2 expression in teeth of Pitx1-/- embryos is not altered, expression of Barx1 decreased in the mesenchyme of the mandibular molars. Furthermore, Pitx1 deletion results in suppression of Tbx1 expression in dental epithelium. Taken together, these results indicate that independent genetic pathways in mandibular and maxillary processes determine tooth development and morphology.
Mitsiadis
Thimios A
TA
Department of Structural and Orofacial Development, Institute of Oral Biology, ZZMK, Faculty of Medicine, University of Zurich, Plattenstrasse 11, 8032 Zurich, Switzerland. thimios.mitsiadis@zzmk.uzh.ch
Drouin
Jacques
J
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008334:Mandible / Q000196:embryology / Q000254:growth & development; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008957:Models, Genetic; D009154:Mutation; D009805:Odontogenesis / Q000235:genetics*; D009924:Organ Culture Techniques; D051761:Paired Box Transcription Factors / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C095587:Barx1 protein, mouse; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; D051761:Paired Box Transcription Factors; D011994:Recombinant Proteins; D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse; D014157:Transcription Factors; C101485:homeobox protein PITX1