Mechanisms for the development of esophageal atresia.
BACKGROUND
There is no universally accepted theory to explain esophageal embryology and the abnormal development that produces esophageal atresia.


METHODS
The impact of Adriamycin administration on the pathogenesis of esophageal atresia was studied in the rat model of VATER association, from embryonic day (ED) 10 to ED 13.


RESULTS
Tissues in the ED10 Adriamycin-exposed embryos displayed less cell proliferation as shown by the reduced population of MIB-5-labelled cells. Cell apoptosis that is characteristic of the normal ED 12 lateral epithelial folds of the foregut (the prospective site of tracheoesophageal septation) was absent in the foregut of the Adriamycin-exposed embryo. Histologic examination of the ED 11-exposed embryo showed the presence of abnormal notochord that was stretched, split, or tethered to the foregut. This contrasts with the normal embryo in which the notochord was localized in close vicinity of the ventral part of the neural tube and separated from the foregut by ample amount of mesenchyme. The abnormal localization of the notochord was accompanied by the lack of down-regulation of the sonic hedgehog (Shh) activity in the prospective site of future tracheoesophageal separation in the exposed ED 12 embryo.


CONCLUSIONS
The authors proposed that the ectopic location of the notochord leads to the disruption in Shh signalling that may underpin the development of esophageal atresia.
Orford
J
J
Department of Surgical Research, Royal Alexandra Hospital for Children, Westmead, and the Department of Paediatrics and Child Health, University of Sydney, Sydney, and the Embryology Unit, Children's Medical Research Institute, Westmead, NSW, Australia.
Manglick
P
P
Cass
D T
DT
Tam
P P
PP
D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin; D004933:Esophageal Atresia / Q000139:chemically induced / Q000196:embryology* / Q000235:genetics; D005333:Fetus / Q000187:drug effects; D005865:Gestational Age; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008565:Membrane Proteins / Q000032:analysis; D009672:Notochord / Q000196:embryology; D000072079:Patched Receptors; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D013723:Teratogens; D015534:Trans-Activators / Q000032:analysis
D000911:Antibodies, Monoclonal; D053823:Hedgehog Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D013723:Teratogens; D015534:Trans-Activators; D004317:Doxorubicin