Aberrant Bmp signaling and notochord delamination in the pathogenesis of esophageal atresia
Open Access
- 26 January 2007
- journal article
- research article
- Published by Wiley in Developmental Dynamics
- Vol. 236 (3), 746-754
- https://doi.org/10.1002/dvdy.21075
Abstract
Human foregut malformation known as esophageal atresia with tracheoesophageal fistula (EA/TEF) occurs in 1 in 4,000 live births with unknown etiology. We found that mice lacking Noggin (Nog−/−) displayed Type C EA/TEF, the most common form in humans, and notochordal defects strikingly similar to the adriamycin-induced rat EA/TEF model. In accord with esophageal atresia, Nog−/− embryos displayed reduction in the dorsal foregut endoderm, which was associated with reduced adhesion and disrupted basement membrane. However, significant apoptosis in the Nog−/− dorsal foregut was not observed. Instead, non-notochordal, likely endodermal, cells were found in Nog−/− notochord, suggesting that Noggin function is required in the notochordal plate for its proper delamination from the dorsal foregut. Notably, ablating Bmp7 function in Nog−/− embryos rescued EA/TEF and notochord branching defects, establishing a critical role of Noggin-mediated Bmp7 antagonism in EA/TEF pathogenesis. Developmental Dynamics 236:746–754, 2007.Keywords
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