title: Palatal adhesion is dependent on Src family kinases and p38MAPK.
abstract: During secondary palate development, palatal shelves adhere to each other in the midline to form a midline epithelial seam leading to palatal closure. Cell-cell and cell-extracellular matrix adhesions, which are mediated by cell adhesion receptors, E-cadherin and integrins, are implicated in the process of adhesion of the palatal shelves. Src family kinases (SFK) function downstream of both receptors. In this study, we focused on the role of SFK in the process of palatal adhesion. During palatal adhesion, the expression of SFK mRNA, as well as localization and quantitation of the protein in the activated form, were examined by real-time qPCR and immunofluorescence. Palatal organ cultures were performed to identify the effect of pharmacological inhibition of SFK on palatal adhesion. Activated SFKs were found to be co-localized with adhesion receptors, E-cadherin and integrins in the palatal medial edge epithelium. Src, Fyn and Yes subfamily members were expressed in the palatal tissue. The expression of SFK mRNA and the quantity of the activated form of the protein were upregulated during palatal adhesion. An SFK inhibitor, PP2, blocked palatal adhesion, but another SFK inhibitor, SU6656 was not inhibitory. However, the combination of SU6656 and either of the p38MAPK inhibitors, SB203580 or BIRB0796, showed similar inhibitory effects on palatal adhesion compared to PP2 alone. The p38MAPK inhibitors alone did not alter palatal adhesion. Real-time qPCR revealed that p38MAPK alpha and delta were elevated during palatal adhesion. This study indicates that palatal cell adhesion is dependent on signaling from integrin receptors and E-cadherin through SFK and p38MAPK.
authors.affiliation: Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver BC, Canada.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kitase
authors.forename: Charles F
authors.initials: CF
authors.lastname: Shuler
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D051379:Mice; D009924:Organ Culture Techniques; D010159:Palate / Q000196:embryology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D019061:src-Family Kinases; D048051:p38 Mitogen-Activated Protein Kinases