title: Impaired expression of myogenic regulatory molecules in the pelvic floor muscles of murine embryos with anorectal malformations.
abstract: OBJECTIVE
  Recent biological studies have elucidated the molecular mechanism of muscle development, in which various regulatory factors (myogenic regulatory factors [MRFs]) play key roles during embryogenesis. To investigate the development of anorectal malformations (ARMs), we studied MRF expressions in myogenic cells in the pelvic floor using murine embryos affected with ARM.
  
  
  METHODS
  Anorectal malformation 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 alfa-actin molecule.
  
  
  RESULTS
  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 to E13.0, leading to hypoplastic pelvic floor muscles.
  
  
  CONCLUSIONS
  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 used for postnatal muscle regeneration to reinforce the pelvic floor muscle function in children with ARM.
authors.affiliation: Division of Surgery, Children's Research Hospital, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan. aoishige@koto.kpu-m.ac.jp
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Aoi
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimotake
authors.forename: Tomoki
authors.initials: T
authors.lastname: Tsuda
authors.forename: Eiichi
authors.initials: E
authors.lastname: Deguchi
authors.forename: Naomi
authors.initials: N
authors.lastname: Iwai
mesh_terms: D000199:Actins / Q000032:analysis / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D001003:Anal Canal / Q000002:abnormalities* / Q000196:embryology; D000818:Animals; D000831:Animals, Newborn; D015820:Cadherins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D000013:Congenital Abnormalities / Q000235:genetics / Q000378:metabolism; D005242:Fecal Incontinence / Q000209:etiology; D005326:Fetal Proteins / Q000032:analysis; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D051379:Mice; D008817:Mice, Mutant Strains; D017570:MyoD Protein / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D032446:Myoblasts / Q000378:metabolism / Q000473:pathology*; D018008:Myogenin / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D018995:Myosin Heavy Chains / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D017773:Pelvic Floor / Q000002:abnormalities* / Q000196:embryology; D010641:Phenotype; D012007:Rectum / Q000002:abnormalities* / Q000196:embryology; D019170:Somites / Q000473:pathology; D013623:Tail / Q000002:abnormalities
chemical_list: D000199:Actins; D015820:Cadherins; D005326:Fetal Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C503801:Myog protein, mouse; D018008:Myogenin; C070896:M-cadherin; D018995:Myosin Heavy Chains