TET1 contributes to neurogenesis onset time during fetal brain development in mice.

Abstract Epigenetic mechanisms are relevant to development and contribute to fetal neurogenesis. DNA methylation and demethylation contribute to neural gene expression during mouse brain development. Ten-eleven translocation 1 (TET1) regulates DNA demethylation by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). TET1 specifically regulates 5hmC in the central nervous system (CNS), including during neurogenesis in the adult brain. However little is known about its function in fetal neurogenesis. In order to evaluate the role of TET1 in fetal brain development, we generated TET1-overexpressing transgenic (TG) mice. TET1 overexpression was confirmed in the brains of fetal mice, and we detected 5hmC overexpression in the TG brains compared to that in the wild type (WT) brains, using a dot-blot assay. In order to observe the role of TET1 in fetal brain development, we examined fetal brain samples at varied time points by using real-time PCR, Western blotting, and Immunofluorescence (IF). We confirmed that TET1 contributes to neurogenesis by upregulating the protein expressions of neuronal markers in the TG mouse brains, as determined by Western blotting. However the cortex structure or brain mass between WT and TG mice showed no significant difference by IF. In conclusion, TET1 makes the start time of neurogenesis earlier in the TG brains compared to that in the WT brains during fetal brain development.