Project description:To investigate the associated with DNA demethylation and neural tube defects (NTDs) with folate deficiency, we etablished mouse embryonic stem cells (mESCs) Sv/129 in folate-deficiency-treated.
Project description:To investigate the associated with abnormal DNA demethylation and neural tube defects (NTDs) with folate deficiency, we etablished mouse embryonic stem cells (mESCs) Sv/129 in folate-deficiency-treated.
Project description:To investigate the associated with abnormal DNA demethylation and neural tube defects (NTDs) with folate deficiency, we etablished mouse embryonic stem cells (mESCs) Sv/129 in folate-deficiency-treated.
Project description:To investigate the associated with the levels of DNA demethylation and neural tube defects (NTDs) with folate deficiency, we etablished mouse embryonic stem cells (mESCs) Sv/129 in folate-deficiency-treated. We then performed gene expression profiling analysis using data obtained from RNA-seq of the cell model.
Project description:Wnt signaling plays a major role in early neural development. An aberrant activation in Wnt/β-catenin pathway leads to defective anteroposterior patterning, resulting in neural tube closure defects (NTDs). Changes in folate metabolism may participate in early embryo fate determination. We report here that in C57BL/6C mouse embryonic stem cells (mESC), folate deficiency activates Wnt/β-catenin pathway by upregulating a chorion-specific transcription factor Gcm1. Specifically, folate deficiency promotes the formation of the Gcm1/β-catenin/T-cell factor (TCF4) complex to regulate the Wnt target gene transactivation through the Wnt-responsive elements. Moreover, the enhanced transcriptional activity of Gcm1 is found to be dependent on CREB binding protein. Lastly, in NTDs mouse models and low folate NTDs human brain samples, Gcm1 and Wnt/β-catenin target genes related to neural tube closure are specifically overexpressed. These results indicate that low folate promotes Wnt/β-catenin signaling via activating Gcm1, leading to aberrant vertebrate neural development
Project description:Neural tube defects (NTDs) are one of the most severe congenital abnormalities. Maternal folate deficiency could impact the occurrence of NTDs. Histone H3 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) expression was significantly downregulated, and low levels of H3K79me2 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Using ChIP-seq assays, we found that a decrease of H3K79me2 downregulates the expression of Shh and Sufu in mouse embryonic stem cells (mESC) under folate deficiency. Our results indicate that abnormal Shh and Sufu genes expression reduced by aberrant Dot1l-mediated H3K79me2 levels could be the cause of NTDs occurrence.
Project description:Folic acid is a nutrient essential for embryonic development. Folate deficiency can cause embryolethality or neural tube defects and orofacial anomalies. Folate receptor 1 (Folr1), is a folate binding protein that facilitates the cellular uptake of dietary folate. Animal studies highlighted critical roles of folate in embryogenesis including orofacial development. Orofacial clefts were observed in the offspring of experimental animals on folic acid-deficient diets. Mice lacking Folr1 (the gene encoding folate receptor 1) also demonstrated a variety of orofacial defects. In order to investigate potential roles of Folr1 during embryogenesis and to identify various genes functionally associated with this receptor, total RNA preparations from gestation day (GD)-9.5, Folr1+/+ and Folr1-/- mouse embryos were used to hybridize messenger RNA arrays, to identify genes expressed in wild type (Folr1+/+) and knockout (Folr1-/-) embryos.
