Aberrant Bmp signaling and notochord delamination in the pathogenesis of esophageal atresia
Article first published online: 26 JAN 2007
Copyright © 2007 Wiley-Liss, Inc.
Volume 236, Issue 3, pages 746–754, March 2007
How to Cite
Li, Y., Litingtung, Y., Ten Dijke, P. and Chiang, C. (2007), Aberrant Bmp signaling and notochord delamination in the pathogenesis of esophageal atresia. Dev. Dyn., 236: 746–754. doi: 10.1002/dvdy.21075
- Issue published online: 22 FEB 2007
- Article first published online: 26 JAN 2007
- Manuscript Accepted: 4 JAN 2007
- National Institutes of Health
- Netherlands Organization for Scientific Research. Grant Number: NWO 916
- Bmp signaling;
- esophageal atresia;
- foregut endoderm;
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. © 2007 Wiley-Liss, Inc.