Adriamycin disruption of the Shh-Gli pathway is associated with abnormalities of foregut development
| Autor: | Vicky A. Cameron, Jacqui Keenan, Qi Bao Quan, Leigh J. Ellmers, Dejan Arsic, Spencer W. Beasley |
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| Rok vydání: | 2004 |
| Předmět: |
Pathology
medicine.medical_specialty animal structures Gestational Age In situ hybridization Biology Rats Sprague-Dawley Mice Esophagus Notochord medicine Animals Hedgehog Proteins RNA Messenger Sonic hedgehog Floor plate Embryogenesis Gene Expression Regulation Developmental Embryo Foregut General Medicine Hedgehog signaling pathway Cell biology Rats Trachea medicine.anatomical_structure Doxorubicin embryonic structures Pediatrics Perinatology and Child Health biology.protein Trans-Activators Surgery Female Signal Transduction |
| Zdroj: | Journal of pediatric surgery. 39(12) |
| ISSN: | 1531-5037 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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