Nuclear architecture in neural plasticity and aging
Dr. Tomohisa Toda
Group leader
Tatzberg 41
01307 Dresden

tomohisa.toda@dzne.de
 +49 351 210 463-710

Research areas/focus

Aging is one of the most critical risk factors for neurological and psychiatric diseases. However, the biological links between physiological aging and pathological development are still largely unknown. Since neural cells in the brain are mostly generated during development with limited capacity of replacement after birth, they need to maintain their identity and function throughout our lives. Our laboratory aims at elucidating this link between the fundamental mechanism underlying the long-term maintenance of neural identity/plasticity and effects of pathological aging on that.Aging is one of the most critical risk factors for neurological and psychiatric diseases. However, the biological links between physiological aging and pathological development are still largely unknown. Since neural cells in the brain are mostly generated during development with limited capacity of replacement after birth, they need to maintain their identity and function throughout our lives. Our laboratory aims at elucidating this link between the fundamental mechanism underlying the long-term maintenance of neural identity/plasticity and effects of pathological aging on that.

 more Infos

Using interdisciplinary approaches with mouse models and stem cell biology, our laboratory focus on cell type-specific nuclear architecture directed by nuclear pore complex proteins (nucleoporins) and nuclear lamins. Cell type-specific nuclear architecture organized by nucleoporins in cooperation with a key transcription factor (TF), work as a structural gatekeeper for the maintenance of neural identity (Toda et al., Cell Stem Cell, 2017). Strikingly, nucleoporins and lamins are the most long-lived proteins in a cell and are known to be damaged during brain ageing. We are investigating a fundamental principle governed by nucleoporin/lamin-directed nuclear architecture in cell type-specific gene regulation, cellular identity/plasticity, and how pathological ageing impairs the underlying mechanism.

Key Publications

Toda T, Parylak SL, Linker SB, Gage FH. The role of adult hippocampal neurogenesis in brain health and disease. Mol Psychiatry. 2019 Jan 20; 24:67-87. doi: 10.1038/s41380-018-0036-2
Toda T, Hsu JY, Linker SB, Hu L, Schafer ST, Mertens J, Jacinto FV, Hetzer MW, Gage FH. Nup153 Interacts with Sox2 to Enable Bimodal Gene Regulation and Maintenance of Neural Progenitor Cells. Cell Stem Cell. 2017 Feb 02; 21:618-634. doi: 10.1016/j.stem.2017.08.012
Toda T, Shinmyo Y, Dinh Duong TA, Masuda K, Kawasaki H. An essential role of SVZ progenitors in cortical folding in gyrencephalic mammals. Sci Rep. 2016 Jul 12; 6 doi: 10.1038/srep29578
Hoshiba Y, Toda T, Ebisu H, Wakimoto M, Yanagi S, Kawasaki H. Sox11 Balances Dendritic Morphogenesis with Neuronal Migration in the Developing Cerebral Cortex. J Neurosci. 2016 May 25; 36:5775-84. doi: 10.1523/JNEUROSCI.3250-15.2016
Masuda K*, Toda T*, Shinmyo Y*, Ebisu H, Hoshiba Y, Wakimoto M, Ichikawa Y, Kawasaki H. (*equal contributions. Pathophysiological analyses of cortical malformation using gyrencephalic mammals. Sci Rep. 2015 Oct 20; 5:15370. doi: 10.1038/srep15370

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