title: Effect of abnormal notochord delamination on hindgut development in the Adriamycin mouse model.
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.
authors: St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan, S-hideaki@marianna-u.ac.jp.
authors: Hideaki
authors: H
authors: Sato
authors: Piotr
authors: P
authors: Hajduk
authors: Shigeyuki
authors: S
authors: Furuta
authors: Munechika
authors: M
authors: Wakisaka
authors: Paula
authors: P
authors: Murphy
authors: Prem
authors: P
authors: Puri
authors: Hiroaki
authors: H
authors: Kitagawa
mesh_terms: D001003:Anal Canal / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism; D000818:Animals; D000071056:Anorectal Malformations; D001006:Anus, Imperforate / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000096:biosynthesis / Q000235:genetics*; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009672:Notochord / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D012313:RNA / Q000235:genetics*; D012007:Rectum / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism; D041623:Tomography, Optical Coherence
chemical_list: D051858:Forkhead Transcription Factors; C486293:Foxf1 protein, mouse; D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D012313:RNA; D004317:Doxorubicin
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