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Introduction The mechanism of intestinal atresia formation remains undefined. Atresia in Fgfr2IIIb−/− mutant mouse embryos is preceded by endodermal apoptosis and involution of the surrounding mesoderm. We have observed that involution of the atretic segment is preceded by down regulation of Sonic hedgehog (SHH) in the endoderm which is a critical organizer of the intestinal mesoderm. We hypothesized that supplementation of Fgfr2IIIb−/− intestinal tracts with exogenous SHH protein prior to atresia formation would prevent involution of the mesoderm and rescue normal intestinal development. Methods In situ hybridization were performed on control and Fgfr2IIIb−/− intestinal tracts for Shh or FoxF1 between embryonic (E) day 11.5 and E12.0. Control and Fgfr2IIIb−/− intestinal tracts were harvested at E10.5 and cultured in media supplemented with FGF10 + SHH, or FGF10 with a SHH-coated bead. In situs were performed at E12.5 for Foxf1. Results Shh and Foxf1 expression were down-regulated during intestinal atresia formation. Media containing exogenous FGF10 + SHH did not prevent colonic atresia formation (involution). A SHH protein point source bead did induce Foxf1 expression in controls and mutants. Discussion Shh and Foxf1 expression are disrupted in atresia formation of distal colon, thereby serving as potential markers of atretic events. Application of exogenous SHH (in media supplement or as a point source bead) is sufficient to induce Foxf1 expression but insufficient to rescue development of distal colonic mesoderm in Fgfr2IIIb−/− mutant embryos. Shh signal disruption is not the critical mechanism by which loss of Fgfr2IIIb function results in atresia formation.

The interpretation of the dexamethasone suppression test in endocrinology and psychiatry depends on several variables. False-positive results can be caused by stress, weight loss, alcohol withdrawal, treatment with diphenylhydantoin, phenobarbital, rifampicin, carbamazepine and lithium. Therapy with spironolactone, naloxone, alpha 1-mimetic agents and estrogen can be responsible for an increase in plasma-cortisol concentration. False-negative results are seen in patients with liver disease and can also result from therapy with benzodiazepines at high dosages, indomethacin and possibly methadone and ketoconazole.