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

Yun-Yuan Tai1, Rung-Shu Chen1, Yi Lin1, Thai-Yen Ling24* and Min-Huey Chen134*

Author Affiliations

1 Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, 10002, Taiwan

2 Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 10002, Taiwan

3 Dental Department, National Taiwan University Hospital, Taipei, 10002, Taiwan

4 Research Center of Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, 10002, Taiwan

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Cell Communication and Signaling 2012, 10:34  doi:10.1186/1478-811X-10-34

Published: 23 November 2012



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.


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.


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.

FGF-9; Epithelial invagination; Ectodermal organogenesis; Combined bioengineered organ-ECIS model; FGF-BMP balancing system