Add like
Add dislike
Add to saved papers

A role for sonic hedgehog signaling in the pathogenesis of human tracheoesophageal fistula.

BACKGROUND/PURPOSE: Many theories of the pathogenesis of esophageal atresia with tracheoesophageal fistula (EA/TEF) have been proposed, but no specific mechanism has been demonstrated. The authors previously reported data suggesting a respiratory origin of the fistula tract in the rat model and in humans. Sonic hedgehog (Shh) "knockout" mice have the VACTERL association, and thus it was hypothesized that defects in Shh signaling may exist in the human neonatal EA/TEF fistula tract.

METHODS: With IRB approval, human proximal esophageal pouch and distal fistula samples were removed at the time of standard repair of EA/TEF in accordance with what the surgeons deemed appropriate in preparation for anastomosis. Tissues were processed for HE, reverse-transcriptase polymerase chain reaction (RT-PCR), and immunohistochemistry. Normal embryonic lung cDNA was used as a positive control for the RT-PCR reactions.

RESULTS: As expected, Shh was present by immunohistochemistry in the proximal esophageal pouch, but was specifically absent in the distal fistula tract. Gli-1, -2, and -3 (all intracellular mediators of Shh signaling) were present in the proximal pouch and distal esophagus by RT-PCR.

CONCLUSIONS: The absence of Shh signaling in the developing fistula tract of the human neonate was surprising given that Shh normally is present in esophagus and other gut components. These results support the conclusion that the fistula tract is not an esophaguslike structure, despite both its histologic appearance and its use as an esophageal replacement. Also, like in Shh-null mutant mice, aberrant Shh signaling may play a critical role in the pathogenesis of EA/TEF in humans.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app