abnormal notochord branching is associated with foregut malformations in the adriamycin treated mouse model脊索异常分支与前肠畸形的阿霉素治疗小鼠模型.pdfVIP

Abnormal Notochord Branching Is Associated with Foregut Malformations in the Adriamycin Treated Mouse Model 1,2 1,2 2 1 Piotr Hajduk , Hideaki Sato , Prem Puri , Paula Murphy * 1 Zoology Department, School of Natural Sciences, University of Dublin, Trinity College, Dublin, Ireland, 2 National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland Abstract Oesophageal atresia (OA) and tracheooesophageal fistula (TOF) are relatively common human congenital malformations of the foregut where the oesophagus does not connect with the stomach and there is an abnormal connection between the stomach and the respiratory tract. They require immediate corrective surgery and have an impact on the future health of the individual. These abnormalities are mimicked by exposure of rat and mouse embryos in utero to the drug adriamycin. The causes of OA/TOF during human development are not known, however a number of mouse mutants where different signalling pathways are directly affected, show similar abnormalities, implicating multiple and complex signalling mechanisms. The similarities in developmental outcome seen in human infants and in the adriamycin treated mouse model underline the potential of this model to unravel the early embryological events and further our understanding of the processes disturbed, leading to such abnormalities. Here we report a systematic study of the foregut and adjacent tissues in embryos treated with adriamycin at E7 and E8 and analysed between E9 and E12, comparing morphology in 3D in 149 specimens. We describe a spectrum of 8 defects, the most common of which is ventral displacement and branching of the notochord (in 94% of embryos at E10) and a close spatial correspo