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We currently lack a comprehensive understanding of the mechanisms underlying neural tube formation and their contributions to neural tube defects (NTDs). Developing a model to study such a complex morphogenetic process, especially one that models human-specific aspects, is critical. Three-dimensional, human embryonic stem cell (hESC)-derived neural rosettes (NRs) provide a powerful resource for in vitro modeling of human neural tube formation. Epigenomic maps reveal enhancer elements unique to NRs relative to 2D systems. A master regulatory network illustrates that key NR properties are related to their epigenomic landscapes. We found that folate-associated DNA methylation changes were enriched within NR regulatory elements near genes involved in neural tube formation and metabolism. Our comprehensive regulatory maps offer insights into the mechanisms by which folate may prevent NTDs. Lastly, our distal regulatory maps provide a better understanding of the potential role of neurological-disorder-associated SNPs.
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http://dx.doi.org/10.1016/j.celrep.2017.07.036 | DOI Listing |
PLoS One
September 2025
Children's Health Research Institute, Victoria Research Labs, London, Ontario, Canada.
Loss of actin cytoskeleton control can hinder integral developmental and physiological processes and can be the basis for a subset of developmental defects. SHROOM3 is an actin binding protein, best characterized as being essential for neural tube closure in vertebrates. Shroom3 expression has also been identified in the developing heart, with some associated congenital heart defects.
View Article and Find Full Text PDFToxicol Lett
September 2025
Mammalian Embryology, Department of Life Science, Faculty of Science and Engineering, Kindai University 3-4-1, Kowake, Higashiosaka, Osaka 577-8501, Japan. Electronic address:
Autism spectrum disorder (ASD) is a developmental disability characterized by impaired social communication and repetitive behaviors, and environmental and genetic factors are involved in its onset. The use of the antiepileptic drug valproic acid (VPA) during pregnancy is associated with neural tube defects and developmental disorders in the fetus. In this study, we aimed to identify abnormalities in cortical morphogenesis owing to prenatal VPA exposure and to elucidate the abnormalities in brain function associated with these abnormalities, particularly by comparing multiple and single environments.
View Article and Find Full Text PDFJ Neurosci Methods
September 2025
Bioengineering College of Chongqing University, Chongqing University Central Hospital (Chongqing Emergency Medical Center), Chongqing, China; Chongqing Key Laboratory of Emergency Medicine, Chongqing, China. Electronic address:
Background: Current neurovascular unit isolation requires processing brain microvascular endothelial cells (BMECs) and neurons from separate animals, preventing concurrent analysis of neurovascular crosstalk within identical genetic/physiological contexts.
New Methods: We developed an enzymatic digestion/bovine serum albumin density gradient technique that enables the simultaneous isolation of neural tissue and microvascular segments from individual mice. The neural tissue was filtered and centrifuged for primary cortical neuron culture on poly-L-lysine-coated plates.
Eur J Nutr
September 2025
Nutritional Biomarker Laboratory, MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Background: The UK has a high and increasing prevalence of folate deficiency. The decision to start mandatory folic acid fortification has not yet been implemented. Concern has been raised about the effect of high folate on vitamin B12 status.
View Article and Find Full Text PDFACS Nano
September 2025
Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China.
An interactive bidirectional relationship between periodontitis and diabetes poses great challenges for the treatment of diabetic periodontitis in clinical practice. The hyperglycemic inflammatory periodontal microenvironment is characterized by oxidative damage, chronic invasive infection, excessive inflammation, unbalanced immunomodulation, progressive neuropathy, diabetic vasculopathy, and uncoupled bone resorption and formation responses. The neuromodulation strategy holds great potential to mediate and coordinate temporally the complex microenvironment for diabetic periodontal regeneration.
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