2004 Fiscal Year Final Research Report Summary
DEVELOPMENTAL STUDY OF PELVIC FLOOR MUSCLES IN ANORECTAL MALFORMATIONS
| Project/Area Number |
13557146
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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 | 展開研究 |
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| Research Field |
Pediatric surgery
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| Research Institution | KYOTO PREFECTURAL UNIVERSITY OF MEDICINE |
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Principal Investigator |
SHIMOTAKE Takashi KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, CHILDREN RESEARCH HOSPITAL, DIVISION OF SURGERY, 医学研究科, 助手 (90254341)
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| Project Period (FY) |
2001 – 2004
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| Keywords | ANORECTAL MALFORMATIONS / DEVELOPMENT / EMBRYOGENESIS / PELVIC FLOOR MUSCLE |
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| Research Abstract |
Recent biological studies have elucidated the molecular mechanism of muscle development, in which various regulatory factors (MRFs) play key roles during embryogenesis. To investigate the development of anorectal malformations (ARM), we studied MRF expressions in myogenic cells in the pelvic floor using murine embryos affected with ARM. ARM embryos were obtained from the 10.5th embryonal day (E10.5) to the 7.0th postnatal day (D7.0) in a natural mutant strain (Sd/+,RSV/Le). Serial frozen sections were prepared for immunohistochemistry using specific antibodies to M-cadherin, myoD, Myogenin, myosin heavy chain, and α-actin molecule. In normal mice, embryonal caudal somites differentiated into myogenic stem cells and migrated to the pelvic floor between E11.0 and E14.0. In the ARM mice, however, caudal somites were irregularly arranged and MRF expressions in myogenic cells were markedly decreased in the dorsocaudal region at E11.5-13.0, leading to hypoplastic pelvic floor muscles. The maldevelopment of pelvic floor muscles in ARM is derived from a deficient supply of myogenic stem cells, with impaired MRF expression. These results suggest that myogenic stem cells, available from bone marrow contents, may be utilized for postnatal muscle regeneration to reinforce the pelvic floor muscle function in children with ARM.
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