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Effect of abnormal notochord delamination on hindgut development in the Adriamycin mouse model

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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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Authors and Affiliations

  1. St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan

    Hideaki Sato, Shigeyuki Furuta, Munechika Wakisaka & Hiroaki Kitagawa

  2. Department of Paediatric Surgery, Our Lady’s Children’s Hospital, Dublin, Ireland

    Piotr Hajduk

  3. Zoology Department, Trinity College Dublin, Dublin, Ireland

    Paula Murphy

  4. National Children’s Research Centre, Our Lady’s Children’s Hospital, Dublin, Ireland

    Prem Puri

Authors
  1. Hideaki Sato
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  2. Piotr Hajduk
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  3. Shigeyuki Furuta
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  4. Munechika Wakisaka
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  5. Paula Murphy
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  6. Prem Puri
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  7. Hiroaki Kitagawa
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Correspondence to Hideaki Sato.

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Sato, H., Hajduk, P., Furuta, S. et al. Effect of abnormal notochord delamination on hindgut development in the Adriamycin mouse model. Pediatr Surg Int 29, 1209–1216 (2013). https://doi.org/10.1007/s00383-013-3386-5

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  • DOI: https://doi.org/10.1007/s00383-013-3386-5

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