Involvement of c-Fos proto-oncogene during palatal fusion and interdigital space formation in the rat

c-Fos is an indispensable proto-oncogene product in the developmental process and a key factor in the proliferation of normal and neoplastic cells. It is also implicated in triggering epithelial-fibroblastoid cell conversion and the induction of apoptosis. To clarify the role of c-Fos in the life span of rat embryonic cells, we examined the disappearance of the medial edge epithelium (MEE) of the palatal shelf on palatal fusion and formation of the interdigital web. Using immunohistochemical techniques with anti-c-Fos antibody and a TdT-mediated dUTP-digoxigenin nick end labeling (TUNEL) method, we compared the pattern of c-Fos-positive cells and DNA fragmentation. To investigate the epithelial-mesenchymal transformation, transforming growth factor (TGF)-β3 was examined in both regions. During palatal fusion, c-Fos was detected in the nuclei of MEE cells just before the elevation of the palatal shelf and strongly stained at the MEE remaining in the center of the palate. c-Fos became undetectable in accordance with the disruption of the medial edge epithelium. We also immunohistochemically recognized the colocalization of c-Fos and TGF-β3 in the MEE. However, DNA fragmentation was not observed at the center of fusion. Considered together, cell disappearance at the fusion site was suggested to reflect epithelial-mesenchymal transformation. In contrast, mesenchymal cells of the interdigital web and the chondrocytes of the digit expressing c-Fos appeared to be the hallmark of programmed cell death and TGF-β3 could not be found in the interdigital mesenchyme. c-Fos in the interdigital space was detected more proximal than DNA fragmentation detection, suggesting that c-Fos acted at the upper stream of apoptosis. Our results support the involvement of c-Fos in the physiological process of cell transformation during palatogenesis and apoptosis during the interdigital formation. c-Fos may trigger a cell specific signal during organogenesis, especially transformation of epithelial cells and apoptosis of mesenchymal cells.