Division of Developmental Neurobiology

Projects

Neurodevelopmental disorders affect 3-8% of individuals in Japan and have a high impact on healthcare systems, economic development, and society. The mechanisms underlying these disorders are poorly understood, hindering the development of treatments and diagnostics. Defects in neocortical development can cause neurodevelopmental disorders. In particular, the evolutionary expansion of the human neocortex underlies higher cognitive abilities and their related disorders. Therefore, studying the mechanisms of neocortical development and evolution will improve our understanding of neurodevelopmental disorders and provide better treatments.

Members

: Takashi Namba Professor

Our group is interested in the developmental cellular dynamics that give rise to the complex architecture of the mammalian brain. One important question is how the human brain expanded in size during evolution. We study how neural stem/progenitor cells acquired their massive proliferative capacity in human brain evolution and how these cellular mechanisms contributed to the evolution of the human brain and the etiology of neurodevelopmental disorders.

: Naoki Yahata Lecturer

The aim of my research is a class of neurodevelopmental disorders arising from mitochondrial DNA mutations. Using iPS cells and genome editing technologies, I develop disease models to study the neuropathology of mitochondrial diseases and potential therapeutic approaches.

Main publications

Xing L, Gkini V, Nieminen AI, Zhou HC, Aquilino M, Naumann R, Reppe K, Tanaka K, Carmeliet P, Heikinheimo O, Pääbo S, Huttner WB, Namba T. Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development. Nat Commun 15:3468, 2024.
Jones AG, Aquilino M, Tinker RJ, Duncan L, Jenkins Z, Carvill GL, DeWard SJ, Grange DK, Hajianpour MJ, Halliday BJ, Holder-Espinasse M, Horvath J, Maitz S, Nigro V, Morleo M, Paul V, Spencer C, Esterhuizen AI, Polster T, Spano A, Gómez-Lozano I, Kumar A, Poke G, Phillips III JA, Underhill HR, Gimenez G, Namba T, Robertson SP. Clustered de novo Start-Loss Variants in GLUL Result in a Developmental and Epileptic Encephalopathy via Stabilization of Glutamine Synthetase. Am J Hum Genet 111:729-741, 2024.
Namba T, Dóczi J, Pinson A, Xing L, Kalebic N, Wilsch-Bräuninger M, Long K, Vaid S, Lauer J, Bogdanova A, Borgonovo B, Shevchenko A, Keller P, Drechsel D, Kurzchalia T, Wimberger P, Chinopoulos C, Huttner WB. Human-specific ARHGAP11B amplifying basal progenitors in developing neocortex operates in mitochondria to enhance glutaminolysis. Neuron 105:867-881, 2020.
Vaid S, Camp JG, Hersemann L, Eugster Oegema C, Heninger AK, Winkler S, Brandl H, Sarov M, Treutlein B, Huttner WB, Namba T. A novel population of Hopx-dependent basal radial glial cells in the developing mouse neocortex. Development 145: dev169276, 2018.

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