title: Adriamycin disruption of the Shh-Gli pathway is associated with abnormalities of foregut development.
abstract: BACKGROUND
  The hedgehog signalling pathway appears to have a crucial role in the embryogenesis of the foregut in vertebrates. Sonic hedgehog (Shh) protein and gene are involved in the differentiation of many organ systems such as notochord, floor plate, and limbs; development of the left-right axis in vertebrates; and differentiation of trachea and esophagus from the primitive foregut.
  
  
  METHODS
  The prenatal exposure of Sprague-Dawley fetal rats to Adriamycin between days 6 and 9 of gestation was used to induce esophageal atresia and tracheoesophageal fistula. Embryos were harvested by cesarean section on gestational days 11 to 15. Embryos were examined by microscopy, dissection, and serial histology. In situ hybridization was used to study Shh gene expression in the rat embryos.
  
  
  RESULTS
  In situ hybridization showed that the pattern and level of Shh gene expression are affected by Adriamycin. Adriamycin-treated rats have deformed notochord and undivided foregut, and some of the embryos had a lack of the dorso-ventral patterning of Shh expression seen in control embryos.
  
  
  CONCLUSIONS
  These results are consistent with the hypothesis that Adriamycin influences the Shh signalling pathway, resulting in disruption of normal development of the foregut.
authors.affiliation: Department of Paediatric Surgery, Christchurch School of Medicine, Christchurch, New Zealand.
authors.forename: Dejan
authors.initials: D
authors.lastname: Arsic
authors.forename: Vicky
authors.initials: V
authors.lastname: Cameron
authors.forename: Leigh
authors.initials: L
authors.lastname: Ellmers
authors.forename: Qi Bao
authors.initials: QB
authors.lastname: Quan
authors.forename: Jacqui
authors.initials: J
authors.lastname: Keenan
authors.forename: Spencer
authors.initials: S
authors.lastname: Beasley
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000494:pharmacology*; D004947:Esophagus / Q000187:drug effects* / Q000196:embryology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005865:Gestational Age; D053823:Hedgehog Proteins; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects* / Q000196:embryology*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000187:drug effects* / Q000235:genetics
chemical_list: D053823:Hedgehog Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D004317:Doxorubicin