PAX9-DEFICIENT MICE LACK PHARYNGEAL POUCH DERIVATIVES AND TEETH AND EXHIBIT CRANIOFACIAL AND LIMB ABNORMALITIES

Pax genes have been shown to play important roles in mammalian develop ment and organogenesis. Pax9, a member of this transcription factor fa mily, 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 genera ted Pax!, deficient mice and show that Pax9 is essential for the devel opment of a variety of organs and skeletal elements. Homozygous Pax9-m utant mice die shortly after birth, most likely as a consequence of a cleft secondary palate. They lack a thymus, parathyroid glands, and ul timobranchial bodies, organs which are derived from the pharyngeal pou ches. 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 Pax 9-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 ra nge of organ primordia.