Fibroblast growth factor signaling in the developing XXXX .

@entity632 @entity49090 @entity4501 @entity1152 @entity11943 @entity10494 @entity33187 @entity35
BACKGROUND/PURPOSE: The @entity632 -induced @entity35 model of @entity1152 and @entity4501 (EA/ @entity49090 ) provides a reliable system for the study of EA/ @entity49090 pathogenesis. The authors previously hypothesized that faulty branching lung morphogenesis pathways were a critical component of its pathogenesis. The authors have found evidence for faulty fibroblast growth factor (FGF) signaling related to epithelial-mesenchymal interactions in the fistula tract. To better define FGF signaling, the differential expression of FGF ligands and their receptors between lung, fistula tract, and esophagus are described. METHODS: Time-dated pregnant, @entity35 were injected with @entity632 (2 mg/kg intraperitoneally) on days 6 through 9 of gestation. Tissues were processed for histology and reverse transcriptase polymerase chain reaction. @entity10494 were measured from whole lung, fistula tract, and esophagus of @entity49090 or normal embryos. Expression of FGF2RIIIb and FGF2RIIIc receptors was measured in isolated epithelium and mesenchyme of lung and fistula tract of @entity49090 embryos as well as lung and esophagus from normal controls. RESULTS: @entity10494 mRNA was present in the fistula tract and normal and @entity632 -exposed lung but absent from whole esophagus. Interestingly, @entity11943 mRNA was present only in normal lung. @entity33187 was present in all tissues examined. FGF2RIIIb mRNA was absent in fistula mesenchyme but present in all other tissues examined. However, the splice variant FGF2RIIIc mRNA was present in all tissues examined. CONCLUSIONS: These findings support defective FGF signaling in the @entity35 model of @entity49090 . Absence of @entity11943 mRNA in @entity632 -exposed tissues suggests the primary effect of @entity632 may be to inhibit @entity11943 expression. Moreover, absence of FGF2RIIIb in fistula mesenchyme may be caused by loss of positive feedback from @entity11943 , its normal obligate ligand. Understanding these specific defects in FGF signaling may provide insight into faulty mechanisms of @entity49090 .
