Formation of duodenal atresias in fibroblast growth factor receptor 2IIIb-/- mouse embryos occurs in the absence of an endodermal plug.
OBJECTIVE
Duodenal atresia in humans has been hypothesized to arise from a failure of the duodenal lumen to recanalize after formation of an endodermal plug. Recently, mutations in the fibroblast growth factor receptor 2 gene (Fgfr2IIIb) have been shown to cause atretic defects of the duodenum in mice. However, work in rats suggests that murine species do not form an endodermal plug during normal duodenal development. These lines of data led us to hypothesize that mice are able to form a duodenal atresia in the absence of an endodermal plug. To test this hypothesis, we examined duodenal development in wild-type and Fgfr2IIIb-/- embryos.


METHODS
Paraffin sections were generated for H&E, E-cadherin, or terminal deoxynucleotidyl transferase-mediated X-dUTP nick end labeling staining from Fgfr2IIIb-/- and wild-type embryos between embryonic days (E) 10.5 and E14.5. Sections were photographed and reconstructed into 3-dimensional display using Adobe Photoshop and Amira Visage software.


RESULTS
Normal mouse duodenum does not form an endodermal plug, although a plug does form in the pyloric region of the stomach at E14.5. Fgfr2IIIb-/- embryos experience significant apoptosis in the duodenal region at E10.5, followed by the disappearance of the endoderm in the atretic precursor by E11.5. Thereafter, the mesoderm of the atretic precursor involutes over the next 2 days in the absence of further apoptosis. Interestingly, an endodermal plug was not observed at any point during the formation of a duodenal atresia.


CONCLUSIONS
These results suggest that duodenal atresia in the Fgfr2IIIb-/- model does not arise from persistence of an epithelial plug. Rather it appears to result from the loss of the endoderm because of apoptosis very early in development.
Section of Pediatric Surgery, Department of Surgery, University of Wisconsin SMPH Madison, Wis 53792, USA.
Robert A
RA
Botham
Marta
M
Franco
Amy L
AL
Reeder
Anastasia
A
Lopukhin
Kohei
K
Shiota
Shigehito
S
Yamada
Peter F
PF
Nichol
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004195:Disease Models, Animal; D004380:Duodenal Obstruction / Q000196:embryology* / Q000235:genetics; D004386:Duodenum / Q000196:embryology*; D004707:Endoderm / Q000196:embryology*; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007409:Intestinal Atresia; D051379:Mice / Q000196:embryology* / Q000235:genetics; D018345:Mice, Knockout; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics
D005819:Genetic Markers; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor