Effect of Abnormal Notochord Delamination on Hindgut Development in the Adriamycin Mouse Model

Overview

Journal Pediatr Surg Int

Specialties General Surgery
Pediatrics

Date 2013 Aug 27

PMID 23975021

Authors

Hideaki Sato

Piotr Hajduk

Shigeyuki Furuta

Munechika Wakisaka

Paula Murphy

Prem Puri

Hiroaki Kitagawa

Affiliations

Soon will be listed here.

Abstract

Background: Adriamycin mouse model (AMM) is a model of VACTERL anomalies. Sonic hedgehog (Shh) pathway, sourced by the notochord, is implicated of anorectal malformations. We hypothesized hindgut anomalies observed in the AMM are the result of abnormal effect of the notochord.

Methods: Time-mated CBA/Ca mice received two intraperitoneal injections of Adriamycin (6 mg/kg) or saline as control on embryonic day (E) 7 and 8. Fetuses were harvested from E9 to E11, stained following whole mount in situ hybridization with labeled RNA probes to detect Shh and Fork head box F1(Foxf1) transcripts. Immunolocalization with endoderm marker Hnf3β was used to visualize morphology. Embryos were scanned by OPT to obtain 3D representations of expressions.

Results: In AMM, the notochord was abnormally displaced ventrally with attachment to the hindgut endoderm in 71 % of the specimens. In 32 % of the treated embryos abnormal hindgut ended blindly in a cystic structure, and both of types were remarked in 29 % of treated embryos. Endodermal Shh and mesenchymal Foxf1 genes expression were preserved around the hindgut cystic malformation.

Conclusions: The delamination of the developing notochord in the AMM is disrupted, which may influence signaling mechanisms from the notochord to the hindgut resulting in abnormal patterning of the hindgut.

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