Journal
DEVELOPMENTAL DYNAMICS
Volume 236, Issue 3, Pages 746-754Publisher
WILEY
DOI: 10.1002/dvdy.21075
Keywords
Nmp signaling; Noggin; esophageal atresia; foregut endoderm; notochord
Categories
Ask authors/readers for more resources
Human foregut malformation known as esophageal atresia with tracheoesophageal fistula (EA/TEF) occurs in I 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available