Is there a Role for Activated Akt in Palatogenesis

Overview

Context of   Is there a Role for Activated Akt in Palatogenesis project at University of Dundee

TGF-β3 plays an important role in palatogenesis. The TGFβ-3 homozygous null (-/-) mouse has a cleft palate and treatment of palatal shelves from these knockout mice, ex vivo, with TGFβ-3 causes the palatal shelves to fuse.

 TGFβ-3 may signal via two pathways; the SMAD pathway or the PI-3 kinase/Akt pathway. Blocking of the PI-3 kinase pathway by the inhibitor LY294002 causes the medial edge epithelium to persist in the midline and the basal lamina to remain intact (Kang and Svoboda, 2002), thus no palatal fusion is seen. Epithelial cells of the midline are seen to disappear after fusion and one of the proposed mechanisms for this is epithelial-mesenchymal transition (EMT) which requires PI-3 kinase activity.

 Other possible mechanisms include cell migration and apoptosis. The project will also look for evidence of these events using scratch assays for cell migration and immunocytochemistry with the PAPR-1 antibody for apoptosis.