TY - JOUR
T1 - Expression of DNMT1 in neural stem/precursor cells is critical for survival of newly generated neurons in the adult hippocampus
AU - Noguchi, Hirofumi
AU - Kimura, Ayaka
AU - Murao, Naoya
AU - Matsuda, Taito
AU - Namihira, Masakazu
AU - Nakashima, Kinichi
N1 - Funding Information:
We thank Y. Bessho, T. Matsui, Y. Nakahata, T. Imamura and S. Katada for valuable discussions and M.E. Greenberg and Z. Zhou for sharing reagents. We are grateful to R. Jaenisch for Dnmt1 flox mice, R. Kageyama for Nestin-CreER T2 mice. We also appreciate the members of our laboratories, in particular T. Sanosaka and B. Juliandi for technical help and suggestions, A.M.D. Adefuin and M.C. Sanosaka for writing this manuscript and experimental support and C. Soldati for establishment of adult NS/PCs. We would like to thank I. Smith for helpful comments and grammatical corrections on the manuscript. Furthermore, we are very grateful to M. Tano and Y. Nakagawa for their excellent secretarial assistance. We appreciate the technical assistance from The Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences. This work was funded by Core Research for Evolutional Science and Technology (CREST) from Japan Science and Technology Agency . H.N. received funding from a Grant-in-Aid for JSPS Fellows (no. 13J09870 ).
Publisher Copyright:
© 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neures.2015.01.014
DO - 10.1016/j.neures.2015.01.014
M3 - Article
C2 - 25659757
AN - SCOPUS:84928215504
SN - 0168-0102
VL - 95
SP - 1
EP - 11
JO - Neuroscience Research
JF - Neuroscience Research
ER -