TGF-β Mediated Cell Proliferation and Rearrangement in Palate Formation

Objectives: Cleft palate is one of the most common congenital birth defects and often requires years of treatment involving different specialists and several surgeries to repair. Previous work from our laboratory and others has shown that TGF-β signaling plays a prominent role in palate development and that abnormal TGF-β signaling causes cleft palate in both humans and mice. Specifically, loss of TGF-β receptor 2 (TGFβR2) leads to a proliferation defect in the neural crest derived palatal mesenchyme, resulting in shortened palatal shelves and a cleft palate. TGF-β mediated extracellular matrix secretion and remodeling has been well documented in several other contexts including cancer metastasis, but it is not well studied in the palate. Here, we aim to determine if changes in the matrix, downstream of TGFβR2, can affect the proliferation and orientation of palatal mesenchyme cells.
Methods: To study the role of TGF-β in palateogenesis, we utilized the Cre/loxP system to ablate TGFβR2 expression in the palatal shelf mesenchyme. Using a combination of organ culture and sectioning, we looked at the localization of several matrix proteins and matrix modulators.
Results: We confirmed the expression of fibronectin and collagen I in the palate. We have also observed rearrangement of the mesenchymal cells upon contact of the two opposing palatal shelves. To study whether cell rearrangement and changes in the matrix are involved in TGFβR2 mediated cell proliferation and palate formation, we are performing live organ imaging in normal and TGβR2 knock out mouse palates.
Conclusions: Our findings underscore the importance of TGF-β signaling in palatogenesis.