Essential Roles of Osr1 and Osr2 in Craniofacial Development

Objectives: We recently showed that the mouse Osr2 gene, which encodes a zinc finger class transcription factor highly homologous to the Drosophila Odd-skipped transcription factor, plays essential roles in secondary palate growth and morphogenesis. Interestingly, many tissues, including those in the craniofacial regions, that express Osr2 during embryonic development were unaffected in the Osr2-/- mutants, suggesting that Osr2 function may be partially complemented by that of the related Osr1 gene. The objective of this research project is to investigate whether Osr1 plays essential roles in craniofacial development and whether Osr1 and Osr2 function partially redundantly. Methods: We have generated and analyzed mutant mice carrying targeted mutations in Osr1 alone or in both Osr1 and Osr2. Results: We found that mice homozygous for a targeted null mutation in the Osr1 gene exhibit retromicrognathia and other unique developmental defects. Histological and skeletal preparations show that the Osr1-/- mutants have hypoplastic mandibles with ectopic cartilage growth from the rostral Meckel's cartilage into the developing tongue. Furthermore, mice homozygous for mutations in both Osr1 and Osr2 exhibit severe mandibular dysgenesis and other cranial structural defects that are not found in mice carrying either mutation. Conclusion: These data indicate that the Osr1 and Osr2 genes play distinct as well as redundant roles in craniofacial development. This research is supported by the NIH/NIDCR grant R01DE13681.