2006 Fiscal Year Final Research Report Summary
Dynamic analysis of Shh and specific receptor in embryologic process of anorectal malformations.
| Project/Area Number |
15390534
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatric surgery
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| Research Institution | Kyoto Prefectural University of Mdicine |
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Principal Investigator |
IWAI Naomi Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Professor, 医学研究科, 教授 (90128695)
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| Co-Investigator(Kenkyū-buntansha) |
KIMURA Osamu Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Associate Professor, 医学研究科, 講師 (10315963)
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| Project Period (FY) |
2003 – 2006
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| Keywords | Anorectal malformations / Embryology / Receptor / Shh / Morphology |
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| Research Abstract |
The aim of this research was to determine the possible role of the retinoid-mediated signaling pathway in the pathogenesis of anorectal malformatins (ARM). We investigated whether all-trans retinoic acid (ATRA) affects the expression pattern of Sonic hedgehog (Shh) and Bone morphogenetic protein (BMP) 4, which play important roles in anorectal morphogenesis in vertebrates.
Pregnant ICR strain mice were fed 100mg/kg of ATRA on the ninth gestigational day (E9). Embryos with or without administration of ATRA were obtained from the uteri between El2 and E16 and were fixed immediately in a 4% paraformaldehyde solution. Frozen sections were evaluated for concentric layers around the endodermal epithelium by II ＆ E stain and immunohistochemistry using antibodies created specifically to act against Shh and BMP4.
More than 95% of the embryos administered ATRA had ARM. In normal hindgut development, Shh from the epithelium induces BMP4 expression in the mesenchyme, which differenciates into the lamina propria and the submucosa. In ARM embryos, expressions of Shh and BMP4, which appear to play a crucial role in organogenesis of the hindgut, were disturbed in the cell signaling pathway between the epithelium and the mesenchyme layers.
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