Bone, cartilage, and teeth of orofacial structures are derived from neural crest cells populating the first pharyngeal arch during embryonic development. Improper patterning and fusion of facial processes results in a variety of orofacial defects including cleft lip and palate (one per 500-1,000 births). The paired-related homeobox genes, Prxl and Prx2, encode DNA binding transcription factors that are highly expressed in the first arch and essential for normal craniofacial development as demonstrated by gene targeting in mice. The mutant mice had numerous craniofacial bones and cartilages that were either missing or malformed. However, the gene-targeted allele deletes an exon which is common to both isoforms and their individual functions could not be determined. The function of the two Prxl protein isoforms on chondrogenic processes will be assessed in micromass (MM) cultures using mandible mesenchyme. Underlying cellular and biochemical processes related to cartilage formation will be thoroughly examined in this culture system. In addition, this study will give insight into 14 highly related homeoproteins, which also play a role in chondrogenesis of the craniofacial region. Hypothesis: Based on their antagonistic biochemical properties, the two Prxl isoforms have opposing effects on cartilage development.
|Mitchell, J M; Hicklin, D M; Doughty, P M et al. (2006) The Prx1 homeobox gene is critical for molar tooth morphogenesis. J Dent Res 85:888-93|