Identification of cis-elements regulating expression of Fgf10 during craniofacial development

Introduction: Fibroblast growth factor 10 (FGF10) is known to be expressed in limb mesenchymal cells and to function as a mesenchymal signaling factor involved in epithelial-mesenchymal interactions during limb development. Fgf10-deficient mice exhibit severe limb truncations and lack of lung formation. Moreover, recent evidence from the knockout mice suggests that Fgf10 serves as an essential regulator of various organs formation during development. We previously isolated the promoter region of Fgf10 containing the 0.7 kb 5'-upstream region from the initiation codon with the 0.9 kb downstream fragment, and examined the transcriptional activity with transgenic mice method using a lacZ-reporter system. The fragment was revealed to be essential for the expression of the reporter gene in developing cartilage of the limb. Objective and Method: To further identify regulatory elements responsible for Fgf10 expression, we have isolated the 6.6 kb 5'-flagment and examined the transcriptional activity in craniofacial region using the same reporter system in this study. Results: Significant expression of the reporter gene was observed in otic vesicle and first branchial arch at E9. At E12.5, expression was detected in inner ear and branchial arches. At E15, the expression of the transgene was detected at olfactory lobe, pericondrium, submandibular and thymus gland. At E18, the expression was detected in papillae of tongue, vibrissae, hair follicles and pericondrium. Conclusion: These results suggest that the 6.6 kb 5'-fragment is able to direct expression of lacZ reporter in various organs in craniofacial region.