FGF-9 accelerates epithelial invagination for ectodermal organogenesis in real time bioengineered organ manipulation

Abstract

Abstract Background Epithelial invagination is important for initiation of ectodermal organogenesis. Although many factors regulate ectodermal organogenesis, there is not any report about their functions in real-time study. Electric cell-substrate impedance sensing (ECIS), a non-invasive, real-time surveillance system, had been used to detect changes in organ cell layer thickness through quantitative monitoring of the impedance of a cell-to-microelectrode interface over time. It was shown to be a good method for identifying significant real-time changes of cells. The purpose of this study is to establish a combined bioengineered organ-ECIS model for investigating the real time effects of fibroblast growth factor-9 (FGF-9) on epithelial invagination in bioengineered ectodermal organs. We dissected epithelial and mesenchymal cells from stage E14.5 murine molar tooth germs and identified the real-time effects of FGF-9 on epithelial-mesenchymal interactions using this combined bioengineered organ-ECIS model. Results Measurement of bioengineered ectodermal organ thickness showed that Fibroblast growth factor-9 (FGF-9) accelerates epithelial invagination in reaggregated mesenchymal cell layer within 3 days. Gene expression analysis revealed that FGF-9 stimulates and sustains early Ameloblastin and Amelogenin expression during odontogenesis. Conclusions This is the first real-time study to show that, FGF-9 plays an important role in epithelial invagination and initiates ectodermal organogenesis. Based on these findings, we suggest FGF-9 can be applied for further study in ectodermal organ regeneration, and we also proposed that the ‘FGF-BMP balancing system’ is important for manipulating the morphogenesis of ectodermal organs. The combined bioengineered organ-ECIS model is a promising method for ectodermal organ engineering and regeneration research.