Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development.

Autor: Xing L; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany. lei.xing@umanitoba.ca.; Department of Biological Sciences, University of Manitoba, Winnipeg, MB, Canada. lei.xing@umanitoba.ca., Gkini V; Neuroscience Center, HiLIFE - Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Nieminen AI; FIMM Metabolomics Unit, Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland., Zhou HC; Center for Cancer Biology (CCB), VIB-KU Leuven, B-3000, Leuven, Belgium., Aquilino M; Neuroscience Center, HiLIFE - Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Naumann R; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany., Reppe K; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany., Tanaka K; Laboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan., Carmeliet P; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, B-3000, Leuven, Belgium.; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, B-3000, Leuven, Belgium.; Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates., Heikinheimo O; Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Pääbo S; Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.; Human Evolutionary Genomics Unit, Okinawa Institute of Science and Technology, Okinawa, Onna-son, Japan., Huttner WB; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany. huttner@mpi-cbg.de., Namba T; Neuroscience Center, HiLIFE - Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland. takashi.namba@helsinki.fi.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Apr 24; Vol. 15 (1), pp. 3468. Date of Electronic Publication: 2024 Apr 24.
DOI: 10.1038/s41467-024-47437-8
Abstrakt: Metabolism has recently emerged as a major target of genes implicated in the evolutionary expansion of human neocortex. One such gene is the human-specific gene ARHGAP11B. During human neocortex development, ARHGAP11B increases the abundance of basal radial glia, key progenitors for neocortex expansion, by stimulating glutaminolysis (glutamine-to-glutamate-to-alpha-ketoglutarate) in mitochondria. Here we show that the ape-specific protein GLUD2 (glutamate dehydrogenase 2), which also operates in mitochondria and converts glutamate-to-αKG, enhances ARHGAP11B's ability to increase basal radial glia abundance. ARHGAP11B + GLUD2 double-transgenic bRG show increased production of aspartate, a metabolite essential for cell proliferation, from glutamate via alpha-ketoglutarate and the TCA cycle. Hence, during human evolution, a human-specific gene exploited the existence of another gene that emerged during ape evolution, to increase, via concerted changes in metabolism, progenitor abundance and neocortex size.
(© 2024. The Author(s).)
Databáze: MEDLINE
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