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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DE016776-03
Application #
7198093
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Hardwick, Kevin S
Project Start
2005-04-01
Project End
2009-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
3
Fiscal Year
2007
Total Cost
$81,706
Indirect Cost
Name
Medical University of South Carolina
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
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