Find in Library

Orofacial clefts affect hundreds of thousands of children worldwide annually and are usually corrected by a series of surgeries extending to childhood. The underlying mechanisms that lead to clefts are still unknown, mainly because of the multifactorial etiology and the myriad of interactions between genes and environmental factors. In the present study, we investigated the role and expression of candidate genes belonging to the <i>FGF/FGFR</i> signaling pathway and <i>FOX</i> family in tissue material obtained from 12 pediatric patients undergoing cleft correction surgery. The expression was investigated using immunohistochemistry (IHC) and chromogenic in-situ hybridization (CISH) in three cell/tissue types—epithelial cells, connective tissue, and endothelial cells. We found elevated expression of <i>FGFR1</i> in epithelial cells while no expression was observed in endothelial cells. Further, our results elucidate the potential pathogenetic role of <i>FGFR1</i> in cellular proliferation, local site inflammation, and fibrosis in cleft patients. Along with <i>bFGF</i> (also called <i>FGF2</i>), <i>FGFR1</i> could play a pro-inflammatory role in clefts. Over-amplification of <i>FGFR2</i> in some patients, along with <i>bFGF</i>, could potentially suggest roles for these genes in angiogenesis. Additionally, increased expression of <i>FOXE1</i> (also called <i>TTF2</i>) contributes to local site inflammation. Finally, zero to low amplification of <i>FOXO1</i> could suggest its potential role in inducing oxidative stress in the endothelium along with reduced epithelial apoptosis.