[en] Neanderthal brains were similar in size to those of modern humans. We sought to investigate potential differences in neurogenesis during neocortex development. Modern human transketolase-like 1 (TKTL1) differs from Neanderthal TKTL1 by a lysine-to-arginine amino acid substitution. Using overexpression in developing mouse and ferret neocortex, knockout in fetal human neocortical tissue, and genome-edited cerebral organoids, we found that the modern human variant, hTKTL1, but not the Neanderthal variant, increases the abundance of basal radial glia (bRG) but not that of intermediate progenitors (bIPs). bRG generate more neocortical neurons than bIPs. The hTKTL1 effect requires the pentose phosphate pathway and fatty acid synthesis. Inhibition of these metabolic pathways reduces bRG abundance in fetal human neocortical tissue. Our data suggest that neocortical neurogenesis in modern humans differs from that in Neanderthals.
Disciplines :
Neurology
Author, co-author :
Pinson, Anneline ; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Xing, Lei ; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Namba, Takashi; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Kalebic, Nereo ; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Peters, Jula ; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Oegema, Christina Eugster ; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Traikov, Sofia; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Reppe, Katrin; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Riesenberg, Stephan ; Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany
Maricic, Tomislav ; Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany
Derihaci, Razvan ; Technische Universität Dresden, Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, 01307 Dresden, Germany
Wimberger, Pauline ; Technische Universität Dresden, Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, 01307 Dresden, Germany
Pääbo, Svante ; Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany
Huttner, Wieland B ; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
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Bibliography
M. Breyl, Triangulating Neanderthal cognition: A tale of not seeing the forest for the trees. Wiley Interdiscip. Rev. Cogn. Sci. 12, e1545 (2021). doi: 10.1002/wcs.1545; pmid: 32918796
D. L. Hoffmann et al., U-Th dating of carbonate crusts reveals Neandertal origin of Iberian cave art. Science 359, 912-915 (2018). doi: 10.1126/science.aap7778; pmid: 29472483
D. Leder et al., A 51, 000-year-old engraved bone reveals Neanderthals' capacity for symbolic behaviour. Nat. Ecol. Evol. 5, 1273-1282 (2021). doi: 10.1038/s41559-021-01487-z; pmid: 34226702
P. Rakic, Evolution of the neocortex: A perspective from developmental biology. Nat. Rev. Neurosci. 10, 724-735 (2009). doi: 10.1038/nrn2719; pmid: 19763105
P. Gunz et al., Neandertal introgression sheds light on modern human endocranial globularity. Curr. Biol. 29, 120-127.e5 (2019). doi: 10.1016/j.cub.2018.10.065; pmid: 30554901
J. H. Lui, D. V. Hansen, A. R. Kriegstein, Development and evolution of the human neocortex. Cell 146, 18-36 (2011). doi: 10.1016/j.cell.2011.06.030; pmid: 21729779
E. Taverna, M. Götz, W. B. Huttner, The cell biology of neurogenesis: Toward an understanding of the development and evolution of the neocortex. Annu. Rev. Cell Dev. Biol. 30, 465-502 (2014). doi: 10.1146/annurev-cellbio-101011-155801; pmid: 25000993
I. Kelava et al., Abundant occurrence of basal radial glia in the subventricular zone of embryonic neocortex of a lissencephalic primate, the common marmoset Callithrix jacchus. Cereb. Cortex 22, 469-481 (2012). doi: 10.1093/cercor/bhr301; pmid: 22114084
X. Wang, J. W. Tsai, B. LaMonica, A. R. Kriegstein, A new subtype of progenitor cell in the mouse embryonic neocortex. Nat. Neurosci. 14, 555-561 (2011). doi: 10.1038/nn.2807; pmid: 21478886
A. Shitamukai, D. Konno, F. Matsuzaki, Oblique radial glial divisions in the developing mouse neocortex induce selfrenewing progenitors outside the germinal zone that resemble primate outer subventricular zone progenitors. J. Neurosci. 31, 3683-3695 (2011). doi: 10.1523/JNEUROSCI.4773-10.2011; pmid: 21389223
M. Betizeau et al., Precursor diversity and complexity of lineage relationships in the outer subventricular zone of the primate. Neuron 80, 442-457 (2013). doi: 10.1016/ j.neuron.2013.09.032; pmid: 24139044
S. A. Fietz et al., OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling. Nat. Neurosci. 13, 690-699 (2010). doi: 10.1038/nn.2553; pmid: 20436478
D. V. Hansen, J. H. Lui, P. R. Parker, A. R. Kriegstein, Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464, 554-561 (2010). doi: 10.1038/ nature08845; pmid: 20154730
V. Borrell, M. Götz, Role of radial glial cells in cerebral cortex folding. Curr. Opin. Neurobiol. 27, 39-46 (2014). doi: 10.1016/ j.conb.2014.02.007; pmid: 24632307
A. Pinson, W. B. Huttner, Neocortex expansion in development and evolution-from genes to progenitor cell biology. Curr. Opin. Cell Biol. 73, 9-18 (2021). doi: 10.1016/j.ceb.2021.04.008; pmid: 34098196
J. F. Coy et al., Molecular cloning of tissue-specific transcripts of a transketolase-related gene: Implications for the evolution of new vertebrate genes. Genomics 32, 309-316 (1996). doi: 10.1006/geno.1996.0124; pmid: 8838793
B. L. Horecker, The pentose phosphate pathway. J. Biol. Chem. 277, 47965-47971 (2002). doi: 10.1074/jbc.X200007200; pmid: 12403765
J. F. Coy, D. Dressler, J. Wilde, P. Schubert, Mutations in the transketolase-like gene TKTL1: Clinical implications for neurodegenerative diseases, diabetes and cancer. Clin. Lab. 51, 257-273 (2005). pmid: 15991799
S. Diaz-Moralli et al., A key role for transketolase-like 1 in tumor metabolic reprogramming. Oncotarget 7, 51875-51897 (2016). doi: 10.18632/oncotarget.10429; pmid: 27391434
A. A. Pollen et al., Molecular identity of human outer radial glia during cortical development. Cell 163, 55-67 (2015). doi: 10.1016/j.cell.2015.09.004; pmid: 26406371
S. A. Fietz et al., Transcriptomes of germinal zones of human and mouse fetal neocortex suggest a role of extracellular matrix in progenitor self-renewal. Proc. Natl. Acad. Sci. U.S.A. 109, 11836-11841 (2012). doi: 10.1073/pnas.1209647109; pmid: 22753484
M. Florio et al., Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion. Science 347, 1465-1470 (2015). doi: 10.1126/science.aaa1975; pmid: 25721503
M. B. Johnson et al., Single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex. Nat. Neurosci. 18, 637-646 (2015). doi: 10.1038/nn.3980; pmid: 25734491
W. Sun et al., TKTL1 is activated by promoter hypomethylation and contributes to head and neck squamous cell carcinoma carcinogenesis through increased aerobic glycolysis and HIF1a stabilization. Clin. Cancer Res. 16, 857-866 (2010). doi: 10.1158/1078-0432.CCR-09-2604; pmid: 20103683
R. Peltonen et al., High TKTL1 expression as a sign of poor prognosis in colorectal cancer with synchronous rather than metachronous liver metastases. Cancer Biol. Ther. 21, 826-831 (2020). doi: 10.1080/15384047.2020.1803008; pmid: 32795237
W. Yuan et al., Silencing of TKTL1 by siRNA inhibits proliferation of human gastric cancer cells in vitro and in vivo. Cancer Biol. Ther. 9, 710-716 (2010). doi: 10.4161/ cbt.9.9.11431; pmid: 20200485
K. Prüfer et al., The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 505, 43-49 (2014). doi: 10.1038/nature12886; pmid: 24352235
J. A. Miller et al., Transcriptional landscape of the prenatal human brain. Nature 508, 199-206 (2014). doi: 10.1038/ nature13185; pmid: 24695229
S. Vaid et al., A novel population of Hopx-dependent basal radial glial cells in the developing mouse neocortex. Development 145, dev169276 (2018). doi: 10.1242/dev.169276; pmid: 30266827
M. A. Martínez-Martínez et al., A restricted period for formation of outer subventricular zone defined by Cdh1 and Trnp1 levels. Nat. Commun. 7, 11812 (2016). doi: 10.1038/ncomms11812; pmid: 27264089
N. Kalebic et al., Neocortical expansion due to increased proliferation of basal progenitors is linked to changes in their morphology. Cell Stem Cell 24, 535-550.e9 (2019). doi: 10.1016/j.stem.2019.02.017; pmid: 30905618
N. Matsumoto, Y. Shinmyo, Y. Ichikawa, H. Kawasaki, Gyrification of the cerebral cortex requires FGF signaling in the mammalian brain. eLife 6, e29285 (2017). doi: 10.7554/ eLife.29285; pmid: 29132503
V. Fernández, C. Llinares-Benadero, V. Borrell, Cerebral cortex expansion and folding: What have we learned?. EMBO J. 35, 1021-1044 (2016). doi: 10.15252/embj.201593701; pmid: 27056680
J. S. Hothersall, M. Gordge, A. A. Noronha-Dutra, Inhibition of NADPH supply by 6-aminonicotinamide: Effect on glutathione, nitric oxide and superoxide in J774 cells. FEBS Lett. 434, 97-100 (1998). doi: 10.1016/S0014-5793(98)00959-4; pmid: 9738459
V. Stepanova et al., Reduced purine biosynthesis in humans after their divergence from Neandertals. eLife 10, e58741 (2021). doi: 10.7554/eLife.58741; pmid: 33942714
C. A. Trujillo et al., Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment. Science 371, eaax2537 (2021). doi: 10.1126/science.aax2537; pmid: 33574182
T. Maricic et al., Comment on "Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment". Science 374, eabi6060 (2021). doi: 10.1126/science.abi6060; pmid: 34648345
T. Namba, J. Nardelli, P. Gressens, W. B. Huttner, Metabolic regulation of neocortical expansion in development and evolution. Neuron 109, 408-419 (2021). doi: 10.1016/ j.neuron.2020.11.014; pmid: 33306962
T. Namba et al., Human-specific ARHGAP11B acts in mitochondria to expand neocortical progenitors by glutaminolysis. Neuron 105, 867-881.e9 (2020). doi: 10.1016/ j.neuron.2019.11.027; pmid: 31883789
M. Florio, T. Namba, S. Pääbo, M. Hiller, W. B. Huttner, A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification. Sci. Adv. 2, e1601941 (2016). doi: 10.1126/sciadv.1601941; pmid: 27957544
F. Röhrig, A. Schulze, The multifaceted roles of fatty acid synthesis in cancer. Nat. Rev. Cancer 16, 732-749 (2016). doi: 10.1038/nrc.2016.89; pmid: 27658529
M. Bastir, A. Rosas, D. E. Lieberman, P. O'Higgins, Middle cranial fossa anatomy and the origin of modern humans. Anat. Rec. 291, 130-140 (2008). doi: 10.1002/ar.20636; pmid: 18213701
S. Herculano-Houzel, The remarkable, yet not extraordinary, human brain as a scaled-up primate brain and its associated cost. Proc. Natl. Acad. Sci. U.S.A. 109 (suppl. 1), 10661-10668 (2012). doi: 10.1073/pnas.1201895109; pmid: 22723358
N. Kalebic et al., Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex. eLife 7, e41241 (2018). doi: 10.7554/eLife.41241; pmid: 30484771
J. Schenk, M. Wilsch-Bräuninger, F. Calegari, W. B. Huttner, Myosin II is required for interkinetic nuclear migration of neural progenitors. Proc. Natl. Acad. Sci. U.S.A. 106, 16487-16492 (2009). doi: 10.1073/pnas.0908928106; pmid: 19805325
K. R. Long et al., Extracellular matrix components HAPLN1, lumican, and collagen I cause hyaluronic acid-dependent folding of the developing human neocortex. Neuron 99, 702-719.e6 (2018). doi: 10.1016/j.neuron.2018.07.013; pmid: 30078576
M. A. Lancaster, J. A. Knoblich, Generation of cerebral organoids from human pluripotent stem cells. Nat. Protoc. 9, 2329-2340 (2014). doi: 10.1038/nprot.2014.158; pmid: 25188634
F. Mora-Bermúdez et al., Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development. eLife 5, e18683 (2016). doi: 10.7554/ eLife.18683; pmid: 27669147
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