Defects in craniofacial development to cleft palate and/or cleft lip in more than 1 out of 1,000 births. Investigation of the molecular mechanisms of craniofacial development will lead to improved diagnosis, treatment, and prevention of these birth defects. The long term objective of this project is to understand the role of the transcription factor Zfhep in craniofacial development. Targeted disruption of the Zfhep/deltaEF-1 gene in mice created cleft secondary palate, hypertrophy of Meckel's cartilage, and perinatal death. However, it is unknown whether these facial defects are due to a direct, or indirect involvement of Zfhep in development. Defining the temporal-spacial expression of Zfhep is an essential step towards determining whether it has a direct role in craniofacial development. The specific goals of this project are to determine the expression pattern of both Zfhep-1 and Zfhep-2 in the mesenchyme and epithelium of the palate, and in Meckel's cartilage during mouse development using both in situ hybridization and immunohistochemistry. We will also investigate the expression of Zfhep during development of tooth buds. We will determine the specific cell types (pre-chrondrocytes, chrondrocytes, or hypertrophy chrondrocytes) expressing Zfhep during development of Meckel's cartilage. The results of this R03 application will provide a complete picture of the temporal and spatial expression pattern of Zfhep during craniofacial development, and demonstrate where Zfhep can have direct effects on development. Subsequent work will investigate the molecular mechanism(s) of Zfhep action during craniofacial development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
1R03DE013614-01A2
Application #
6339467
Study Section
Special Emphasis Panel (ZDE1-WG (02))
Program Officer
Small, Rochelle K
Project Start
2001-03-01
Project End
2003-02-28
Budget Start
2001-03-01
Budget End
2002-02-28
Support Year
1
Fiscal Year
2001
Total Cost
$36,000
Indirect Cost
Name
University of Louisville
Department
Dentistry
Type
Schools of Dentistry
DUNS #
City
Louisville
State
KY
Country
United States
Zip Code
40292
Jin, Jiu-Zhen; Li, Qun; Higashi, Yujiro et al. (2008) Analysis of Zfhx1a mutant mice reveals palatal shelf contact-independent medial edge epithelial differentiation during palate fusion. Cell Tissue Res 333:29-38
Manavella, Pablo A; Roqueiro, Gonzalo; Darling, Douglas S et al. (2007) The ZFHX1A gene is differentially autoregulated by its isoforms. Biochem Biophys Res Commun 360:621-6
Darling, Douglas S; Stearman, Randi P; Qi, Yingchaun et al. (2003) Expression of Zfhep/deltaEF1 protein in palate, neural progenitors, and differentiated neurons. Gene Expr Patterns 3:709-17
Smith, Gregory E; Darling, Douglas S (2003) Combination of a zinc finger and homeodomain required for protein-interaction. Mol Biol Rep 30:199-206
Costantino, Mary E; Stearman, Randi P; Smith, Gregory E et al. (2002) Cell-specific phosphorylation of Zfhep transcription factor. Biochem Biophys Res Commun 296:368-73