<i>Pax9</i>-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities

TLDR

Pax genes are key regulators of mammalian development, with Pax9 expressed in somites, pharyngeal pouches, and mesenchyme that contribute to craniofacial, tooth, and limb formation. The study generated Pax9‑deficient mice to determine Pax9’s essential role in organ and skeletal development. Pax9‑deficient mice die shortly after birth with cleft palate, lack thymus, parathyroid, and ultimobranchial glands, display supernumerary preaxial digits and missing hindlimb flexors, have disrupted craniofacial and visceral skeletons, are edentulous with tooth buds arrested, and show loss of Bmp4, Msx1, and Lef1 expression, confirming Pax9 as a key regulator of diverse organ primordia.

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.