PRX1 AND PRX2 IN SKELETOGENESIS - ROLES IN THE CRANIOFACIAL REGION, INNER-EAR AND LIMBS

Prx1 and Prx2 are closely related paired-class homeobox genes that are expressed in very similar patterns predominantly in mesenchyme, Prx1 loss-of-function mutants show skeletal defects in skull, limbs and ver tebral column (Martin, J, F,, Bradley, A, and Olson, E. N, (1995) Gene s Dev. 9, 1237-1219). We report here that mice in which Prx2 is inacti vated by a lacZ insertion had no skeletal defects, whereas Prx1/Prx2 d ouble mutants showed many novel abnormalities in addition to an aggrav ation of the Prx1 single mutant phenotype. We found defects in externa l, middle and inner ear, reduction or loss of skull bones, a reduced a nd sometimes cleft mandible, and limb abnormalities including postaxia l polydactyly and bent zeugopods, A single, or no incisor was present in the lower jaw, and ectopic expression of Fgf8 and Pax9 was found me dially in the mandibular arch, A novel method to detect beta-galactosi dase activity in hydroxyethylmethacrylate sections allowed detailed an alysis of Prx2 expression in affected structures, Our results suggest a role for Prx genes in mediating epitheliomesenchymal interactions in inner ear and lower jaw In addition, Prx1 and Prx2 are involved in in teractions between perichondrium and chondrocytes that regulate their proliferation or differentiation in the bones of the zeugopods.