Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Spilde, T.L. et al.

Aberrant fibroblast growth factor receptor 2 signalling in esophageal atresia with tracheoesophageal fistula.

BACKGROUND: Although the pathogenesis of esophageal atresia with tracheoesophageal fistula (EA/TEF) remains unknown, it has been shown that despite its esophageal appearance, the fistula tract originates from respiratory epithelium. The authors now hypothesize that defects in fibroblast growth factor ( FGF) signaling contribute to the esophaguslike phenotype of the fistula tract. FGF2R is critical to normal lung morphogenesis and occurs in 2 isoforms (FGF2RIIIb and FGF2RIIIc), each with different ligand-binding specificity. To characterize FGF signaling in the developing EA/TEF, the authors analyzed levels of FGF2R splice variants in experimental EA/TEF. METHODS: The standard Adriamycin-induced EA/TEF model in rats was used. Individual foregut components from Adriamycin-treated and control embryos were processed for real-time, fluorescence-activated semiquantitative reverse transcriptase polymerase chain reaction on gestational days 12.5 and 13. 5. RESULTS: Both fistula tract and Adriamycin-treated or normal esophagus showed significantly lower levels of FGF2RIIIb than either Adriamycin-treated lung buds (E12.5, P =.02; E13.5, P <.005) or normal lung buds (E12.5, P <.005; E13.5, P <.01). At E13.5, the fistula tract had lower levels of FGF2RIIIc than either treated (P <.01) or normal lung (P <.05). CONCLUSIONS: Levels of FGF2R in the developing fistula tract resemble that of distal esophagus rather than developing lung. This defect in FGF2RIIIb signaling may account for the nonbranching, esophaguslike phenotype of the fistula, despite its respiratory origin.[1]

References

Aberrant fibroblast growth factor receptor 2 signalling in esophageal atresia with tracheoesophageal fistula. Spilde, T.L., Bhatia, A.M., Mehta, S.S., Hembree, M.J., Preuett, B.L., Ostlie, D.J., Prasadan, K., Li, Z., Snyder, C.L., Gittes, G.K. J. Pediatr. Surg. (2004) [Pubmed]

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