Aberrant Bmp signaling and notochord delamination in the pathogenesis of esophageal atresia

Y Li, Y Litingtung, P Ten Dijke… - … dynamics: an official …, 2007 - Wiley Online Library
Y Li, Y Litingtung, P Ten Dijke, C Chiang
Developmental dynamics: an official publication of the American …, 2007Wiley Online Library
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 …
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. © 2007 Wiley‐Liss, Inc.
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