The development of the face requires a complex series of interactions between the epithelium and the mesenchyme. The different sets of instructive interactions result in patterning of the facial primordia directly linked to both the development of specific craniofacial structures and the fate of specific cells. Secondary palatal development has 3 specific patterning stages, the growth zone phase, dorsal-ventral patterning of the medial edge epithelium in the midline and the anterior-posterior patterning of the palatal shelf. The MEE are dorsal-ventral patterned such that some cells migrate to the oral or nasal surfaces while others undergo epithelial-mesenchymal transdifferentiation. The cell fate of the MEE is established in a dorsal-ventral orientation and regulation of these fates is highly controlled. Anterior-posterior patterning of the palatal shelves regulates timing of palatal fusion and exhibits spatially distinct regulation of the fusion events. The growth zone, dorsal-ventral and anterior-posterior patterning of the palatal shelves are regulated locally by specific inductive signals. TGF-B3 has been shown to be 1 critical signaling molecule regulating the fate of the MEE during palatogenesis and has led to the hypothesis that;Medial edge epithelial cell differentiation is controlled by autocrine and paracrine mechanisms that establish growth zone, dorsal-ventral and anterior-posterior patterning during palatogenesis. This hypothesis will be tested with 3 specific aims;1.To determine the factors that regulate MEE differentiation during the growth zone phase of palatogenesis and their relationship to the EGF signaling pathway in these cells;2.To characterize the dorsal-ventral patterning of the MEE during the fusion of the palatal shelves as defined by cell adhesion molecules and growth factor receptors that determine the specific fates of different populations of MEE;3) To examine the anterior-posterior patterning of the MEE that defines the different potentials for completion of fusion in the Smad 2 overexpression rescue of the TGF-B3 null mutant. Identification of molecular mechanisms essential to the process of palatal fusion will result in future applications to develop prenatal diagnosis strategies and specific interventions to reduce the incidence of human craniofacial birth defects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE016296-05
Application #
7821437
Study Section
Skeletal Biology Development and Disease Study Section (SBDD)
Program Officer
Scholnick, Steven
Project Start
2006-06-01
Project End
2013-05-31
Budget Start
2010-06-01
Budget End
2013-05-31
Support Year
5
Fiscal Year
2010
Total Cost
$212,542
Indirect Cost
Name
University of British Columbia
Department
Type
DUNS #
251949962
City
Vancouver
State
BC
Country
Canada
Zip Code
V6 1-Z3
Nakajima, Akira; Ito, Yoshihiro; Tanaka, Eiji et al. (2014) Functional role of TGF-? receptors during palatal fusion in vitro. Arch Oral Biol 59:1192-204
Kitase, Yukiko; Shuler, Charles F (2014) Palatal adhesion is dependent on Src family kinases and p38MAPK. Int J Dev Biol 58:335-41
Kitase, Yukiko; Shuler, Charles F (2013) Microtubule disassembly prevents palatal fusion and alters regulation of the E-cadherin/catenin complex. Int J Dev Biol 57:55-60
Kitase, Yukiko; Shuler, Charles F (2012) Multi-layered hypertrophied MEE formation by microtubule disruption via GEF-H1/RhoA/ROCK signaling pathway. Dev Dyn 241:1169-82
Fujita, Tsuyoshi; Alotaibi, Mazen; Kitase, Yukiko et al. (2012) Smad2 is involved in the apoptosis of murine gingival junctional epithelium associated with inhibition of Bcl-2. Arch Oral Biol 57:1567-73
Kitase, Yukiko; Yamashiro, Keisuke; Fu, Katherine et al. (2011) Spatiotemporal localization of periostin and its potential role in epithelial-mesenchymal transition during palatal fusion. Cells Tissues Organs 193:53-63
Nakajima, Akira; Ito, Yoshihiro; Asano, Masatake et al. (2007) Functional role of transforming growth factor-beta type III receptor during palatal fusion. Dev Dyn 236:791-801