title: Expression of DNMT1 in neural stem/precursor cells is critical for survival of newly generated neurons in the adult hippocampus.
abstract: Adult neurogenesis persists throughout life in the dentate gyrus (DG) of the hippocampus, and its importance has been highlighted in hippocampus-dependent learning and memory. Adult neurogenesis consists of multiple processes: maintenance and neuronal differentiation of neural stem/precursor cells (NS/PCs), followed by survival and maturation of newborn neurons and their integration into existing neuronal circuitry. However, the mechanisms that govern these processes remain largely unclear. Here we show that DNA methyltransferase 1 (DNMT1), an enzyme responsible for the maintenance of DNA methylation, is highly expressed in proliferative cells in the adult DG and plays an important role in the survival of newly generated neurons. Deletion of Dnmt1 in adult NS/PCs (aNS/PCs) did not affect the proliferation and differentiation of aNS/PCs per se. However, it resulted in a decrease of newly generated mature neurons, probably due to gradual cell death after aNS/PCs differentiated into neurons in the hippocampus. Interestingly, loss of DNMT1 in post-mitotic neurons did not influence their survival. Taken together, these findings suggest that the presence of DNMT1 in aNS/PCs is crucial for the survival of newly generated neurons, but is dispensable once they accomplish neuronal differentiation in the adult hippocampus.
authors: Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Laboratory of Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan.
authors: Hirofumi
authors: H
authors: Noguchi
authors: Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Ayaka
authors: A
authors: Kimura
authors: Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Laboratory of Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan.
authors: Naoya
authors: N
authors: Murao
authors: Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Taito
authors: T
authors: Matsuda
authors: Molecular Neurophysiology Group, Biomedical Research Institute, AIST, Ibaraki, Japan.
authors: Masakazu
authors: M
authors: Namihira
authors: Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: kin1@scb.med.kyushu-u.ac.jp.
authors: Kinichi
authors: K
authors: Nakashima
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000201:enzymology*
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619381:Dnmt1 protein, mouse
keywords: Adult neurogenesis; DNA methylation; DNA methyltransferase 1; Neural stem cells; Neuronal survival