title: Pax9-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities.
abstract: Pax genes have been shown to play important roles in mammalian development and organogenesis. Pax9, a member of this transcription factor family, is expressed in somites, pharyngeal pouches, mesenchyme involved in craniofacial, tooth, and limb development, as well as other sites during mouse embryogenesis. To analyze its function in vivo, we generated Pax9 deficient mice and show that Pax9 is essential for the development of a variety of organs and skeletal elements. Homozygous Pax9-mutant mice die shortly after birth, most likely as a consequence of a cleft secondary palate. They lack a thymus, parathyroid glands, and ultimobranchial bodies, organs which are derived from the pharyngeal pouches. In all limbs, a supernumerary preaxial digit is formed, but the flexor of the hindlimb toes is missing. Furthermore, craniofacial and visceral skeletogenesis is disturbed, and all teeth are absent. In Pax9-deficient embryos tooth development is arrested at the bud stage. At this stage, Pax9 is required for the mesenchymal expression of Bmp4, Msx1, and Lef1, suggesting a role for Pax9 in the establishment of the inductive capacity of the tooth mesenchyme. In summary, our analysis shows that Pax9 is a key regulator during the development of a wide range of organ primordia.
authors.affiliation: GSF-Research Center for Environment and Health, Institute for Mammalian Genetics, 85764 Neuherberg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Peters
authors.forename: A
authors.initials: A
authors.lastname: Neubüser
authors.forename: K
authors.initials: K
authors.lastname: Kratochwil
authors.forename: R
authors.initials: R
authors.lastname: Balling
mesh_terms: D000818:Animals; D002972:Cleft Palate / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004475:Ectoderm / Q000502:physiology; D005314:Embryonic and Fetal Development; D004707:Endoderm / Q000502:physiology; D005091:Exons; D018507:Gene Expression Regulation, Developmental; D015698:Genomic Library; D006579:Heterozygote; D017880:Limb Deformities, Congenital / Q000235:genetics*; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051764:PAX9 Transcription Factor; D010614:Pharynx / Q000002:abnormalities*; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D014071:Tooth Abnormalities / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D051764:PAX9 Transcription Factor; D014157:Transcription Factors