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

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.Ectodermal organogenesis involves the development of many ectodermal organs including hair, feathers, scales, teeth, beaks, nails, horns and several eccrine glands. Despite diverse forms and functions, ectodermal organs exhibit common developmental features. Originating from adjacent layers of epithelial (ectodermal) and mesenchymal (mesodermal or neural crest) tissues, the first visible sign of most ectodermal organs is a local epithelial thickening termed an ectodermal placode. Next, a condensation of mesenchymal cells, or papilla, forms under the placode. The ectodermal placode then buds into or out of the papilla in a process called epithelial invagination. Subsequent morphogenesis drives further development of the epithelial and mesenchymal components and is associated with epithelial folding and branching. This ultimately determines the final shape and size of ectodermal organs; however, it is epithelial invagination that regulates when and how ectodermal organs develop, a fact with important implications for future organ engineering and regeneration [for review see [1]].Although many factors regulate ectodermal organogenesis, observing their