Abstract
BackgroundNeural tube defects (NTDs) result from failure of neural tube closure during embryogenesis. These severe birth defects of the central nervous system include anencephaly and spina bifida, and affect 0.5–2 per 1,000 pregnancies worldwide in humans. It has been demonstrated that acetylation plays a pivotal role during neural tube closure, as animal models for defective histone acetyltransferase proteins display NTDs. Acetylation represents an important component of the complex network of posttranslational regulatory interactions, suggesting a possible fundamental role during primary neurulation events. This study aimed to assess protein acetylation contribution to early patterning of the central nervous system both in human and murine specimens.MethodsWe used both human and mouse (Cited2 −/−) samples to analyze the dynamic acetylation of proteins during embryo development through immunohistochemistry, western blot analysis and quantitative polymerase chain reaction.ResultsWe report the dynamic profile of histone and protein acetylation status during neural tube closure. We also report a rescue effect in an animal model by chemical p53 inhibition.ConclusionsOur data suggest that the p53‐acetylation equilibrium may play a role in primary neurulation in mammals.
Highlights
The neural tube is the embryonic precursor of the brain and spinal cord, and formation of this structure is a critical process in embryonic development
For an assessment of the acetylation profile during neurulation we turned to the mouse, in which the neurulation process is similar to humans
histone acetyltransferase (HAT), p300, we studied the acetylation profile of mouse embryos from litters carrying a loss-of-function mutation in Cited2 (Bhattacharya et al, 1999)
Summary
The neural tube is the embryonic precursor of the brain and spinal cord, and formation of this structure is a critical process in embryonic development. Mouse mutants implicate a large number of genes in neural tube closure, the molecular basis of NTDs is not well understood in the majority of human cases. Neural tube defects (NTDs) result from failure of neural tube closure during embryogenesis These severe birth defects of the central nervous system include anencephaly and spina bifida, and affect 0.5–2 per 1,000 pregnancies worldwide in humans. It has been demonstrated that acetylation plays a pivotal role during neural tube closure, as animal models for defective histone acetyltransferase proteins display NTDs. Acetylation represents an important component of the complex network of posttranslational regulatory interactions, suggesting a possible fundamental role during primary neurulation events. Results: We report the dynamic profile of histone and protein acetylation status during neural tube closure. Conclusions: Our data suggest that the p53-acetylation equilibrium may play a role in primary neurulation in mammals
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