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

作者：Li Yina; Ying Litingtung; Ten Dijke Peter; Chiang Chin^*

来源：Developmental Dynamics, 2007, 236(3): 746-754.

DOI：10.1002/dvdy.21075

• Nmp signaling
• Noggin
• esophageal atresia
• foregut endoderm
• notochord

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.

• 出版日期2007-3