Abstract:
AIM:In chick embryos, administration of cadmium (Cd) induces ventral body wall defects (VBWD) similar to human omphalocele. It has been shown that failure of proper VBW formation may be due to disruption of somite development during early embryogenesis. In the VBWD chick model, Cd causes abnormal cell death in the somitic region resulting in improperly developed somites and tortuosity of the neural tube. However, the exact molecular mechanisms leading to VBWD still remain unclear. Wnt signaling is crucial during embryogenesis and plays a key role in normal somite formation. The Rho-associated coiled-coil containing protein kinase (ROCK) is involved in the non-canonical Wnt pathway which controls actin cytoskeleton assembly and cell contractility, and contributes to several developmental processes including somitogenesis. ROCK gene expression levels have recently been reported to be significantly decreased in the Cd-induced VBWD chick model. We designed this study to investigate the hypothesis that administration of ROCK inhibitor (Y-27632) in the absence of Cd disrupts somitogenesis and could contribute to the development of VBWD during early embryogenesis. METHODS:After 60 h of incubation chick embryos were transferred from eggs to culture dishes containing 20 μM of Y-27632 for experimental group (Y-27, n = 22) or chick saline for controls (n = 14). Following 24 h in the incubator they were assessed for stage development and gross abnormalities in morphology using the dissecting microscope. Western blot was performed to confirm Y-27632 inhibition of ROCK downstream signaling using an antibody against phosphorylated cofilin-2. RESULTS:20 (90.9 %) embryos from Y-27 group and all controls were alive at examination. Morphological abnormalities were detected in 14 (70 %) Y-27 embryos. Somites appeared improperly developed, flattened in the cranio-caudal direction, and elongated in transverse direction in relation to controls. Chick embryos in Y-27 also presented with tortuosity of the neural tube in the lumbosacral region. Western blot analysis showed inhibition of cofilin-2 phosphorylation in affected embryos in comparison to controls. CONCLUSION:Our study provides evidence that ROCK inhibitor results in the disruption of normal somitogenesis in chick embryos which may contribute to the failure of fusion of the anterior abdominal wall causing VBWD.
journal_name
Pediatr Surg Intjournal_title
Pediatric surgery internationalauthors
Duess JW,Fujiwara N,Corcionivoschi N,Puri P,Thompson Jdoi
10.1007/s00383-012-3202-7subject
Has Abstractpub_date
2013-01-01 00:00:00pages
13-8issue
1eissn
0179-0358issn
1437-9813journal_volume
29pub_type
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journal_title:Pediatric surgery international
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abstract::A new instrument for suction rectal biopsy in infants suspected of having Hirschsprung's disease is described that can be completely dismantled, physically cleaned, lubricated, and heat-sterilised. These attributes are new and are absolutely critical today. The instrument has been used in 60 patients (ca. 180 biopsies...
journal_title:Pediatric surgery international
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journal_title:Pediatric surgery international
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journal_title:Pediatric surgery international
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更新日期:1996-06-01 00:00:00
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更新日期:2009-06-01 00:00:00
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journal_title:Pediatric surgery international
pub_type: 杂志文章
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更新日期:1997-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:1996-06-01 00:00:00
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pub_type: 杂志文章,meta分析,评审
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更新日期:2013-05-01 00:00:00
abstract::The presentation of congenital diaphragmatic hernia (CDH) at birth may fall outside the typical features (cyanosis, tachypnea and respiratory failure), manifesting, instead, also with others pictures that make the diagnosis difficult or even impossible. We report a case of CDH presenting as a pneumothorax and a perfor...
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pub_type: 杂志文章,评审
doi:10.1007/s00383-007-2000-0
更新日期:2008-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s00383-013-3382-9
更新日期:2013-11-01 00:00:00
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pub_type: 杂志文章,多中心研究
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更新日期:2008-06-01 00:00:00
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更新日期:1996-10-01 00:00:00
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