Courtney Haycraft, PhD
The Expression and Function of the Primary Cilium in Murine Tooth Morphogenesis (Start date 8/1/08)
We are investigating the role of cytochrome p450 enzymes in tobacco-related oral carcinogenesis. Our central hypothesis is that CYP1B1 induction in oral mucosa contributes to oral carcinogenesis via metabolic activation of benzo[a]pyrene, which results in DNA adduct formation and mutations in genes such as p53.
Cilia are small organelles expressed on most cells throughout the mammalian body. Loss of cilia or basal body function has been associated with several human disorders including Bardet-Biedl symdrome, Oral-Facial-Digital symdrome I, and Ellis-van Creveld syndrome all of which exhibit defects in tooth patterning (missing or ctopic teeth) and/or tooth structure. Cilia have been shown on both the odontoblasts and ameloblasts during tooth development, although their function is unknown. In agreement with a role for cilia in tooth patterning, mice with a hypomorphic allele of the IFT gene Ift88orpk an extra molar develops. Ift88 null mice die prior to the onset of tooth development. To bypass this lethality, we have generated a conditional null allele of Ift88, which can be deleted by expression of Cre recombinase at various times of tooth development. Using these mice and a Cre recombinase that can be activated at specific times in development, we have begun to examine the patterning and morphogenesis of murine teeth following deletion of cilia using various techniques including histology and in situ hybridization.