Neocortex expansion in development and evolution-from genes to progenitor cell biology.

[en] The evolutionary expansion of the neocortex, the seat of higher cognitive functions in humans, is primarily due to an increased and prolonged proliferation of neural progenitor cells during development. Basal progenitors, and in particular basal radial glial cells, are thought to have a key role in the increased generation of neurons that constitutes a foundation of neocortex expansion. Recent studies have identified primate-specific and human-specific genes and changes in gene expression that promote increased proliferative capacity of cortical progenitors. In many cases, the cell biological basis underlying this increase has been uncovered. Model systems such as mouse, ferret, nonhuman primates, and cerebral organoids have been used to establish the relevance of these genes for neocortex expansion.

Disciplines :

Neurology

Author, co-author :

Pinson, Anneline ; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany. Electronic address: pinson@mpi-cbg.de

Huttner, Wieland B; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany. Electronic address: huttner@mpi-cbg.de

Language :

English

Title :

Neocortex expansion in development and evolution-from genes to progenitor cell biology.

Publication date :

December 2021

Journal title :

Current Opinion in Cell Biology

ISSN :

0955-0674

Publisher :

Elsevier Ltd, England

Volume :

Pages :

9 - 18

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.elsevier.com/content/article/PII:S0955067421000582?httpAccept=text/xml

Funders :

MPG - Max Planck Society [DE]

Funding text :

The authors apologize to all researchers whose work could not be cited because of space limitation. The authors thank Takashi Namba, Nereo Kalebic, Lei Xing, and Samir Vaid for critically reading the manuscript.

Available on ORBi :

since 22 May 2023

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Bibliography

Rakic, P., Evolution of the neocortex: a perspective from developmental biology. Nat Rev Neurosci 10 (2009), 724–735.
Lui, J.H., Hansen, D.V., Kriegstein, A.R., Development and evolution of the human neocortex. Cell 146 (2011), 18–36.
Florio, M., Huttner, W.B., Neural progenitors, neurogenesis and the evolution of the neocortex. Development 141 (2014), 2182–2194.
Lewitus, E., Kelava, I., Kalinka, A.T., Tomancak, P., Huttner, W.B., An adaptive threshold in mammalian neocortical evolution. PLoS Biol, 12, 2014, e1002000.
Stepien, B.K., Naumann, R., Holtz, A., Helppi, J., Huttner, W.B., Vaid, S., Lengthening neurogenic period during neocortical development causes a hallmark of neocortex expansion. Curr Biol, 2020, 4227–4237.
Taverna, E., Götz, M., Huttner, W.B., The cell biology of neurogenesis: toward an understanding of the development and evolution of the neocortex. Annu Rev Cell Dev Biol 30 (2014), 465–502.
Kriegstein, A.R., Götz, M., Radial glia diversity: a matter of cell fate. Glia 43 (2003), 37–43.
Götz, M., Huttner, W.B., The cell biology of neurogenesis. Nat Rev Mol Cell Biol 6 (2005), 777–788.
Kriegstein, A., Noctor, S., Martinez-Cerdeno, V., Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion. Nat Rev Neurosci 7 (2006), 883–890.
Gal, J.S., Morozov, Y.M., Ayoub, A.E., Chatterjee, M., Rakic, P., Haydar, T.F., Molecular and morphological heterogeneity of neural precursors in the mouse neocortical proliferative zones. J Neurosci 26 (2006), 1045–1056.
Tyler, W.A., Haydar, T.F., Multiplex genetic fate mapping reveals a novel route of neocortical neurogenesis, which is altered in the Ts65Dn mouse model of Down syndrome. J Neurosci, 33, 2013 5106–5019.
Haubensak, W., Attardo, A., Denk, W., Huttner, W.B., Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. Proc Natl Acad Sci U S A 101 (2004), 3196–3201.
Miyata, T., Kawaguchi, A., Saito, K., Kawano, M., Muto, T., Ogawa, M., Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells. Development 131 (2004), 3133–3145.
Noctor, S.C., Martinez-Cerdeno, V., Ivic, L., Kriegstein, A.R., Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci 7 (2004), 136–144.
Attardo, A., Calegari, F., Haubensak, W., Wilsch-Bräuninger, M., Huttner, W.B., Live imaging at the onset of cortical neurogenesis reveals differential appearance of the neuronal phenotype in apical versus basal progenitor progeny. PloS One, 3, 2008, e2388.
Hansen, D.V., Lui, J.H., Parker, P.R., Kriegstein, A.R., Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464 (2010), 554–561.
Betizeau, M., Cortay, V., Patti, D., Pfister, S., Gautier, E., Bellemin-Ménard, A., Afanassieff, M., Huissoud, C., Douglas, R.J., Kennedy, H., et al. Precursor diversity and complexity of lineage relationships in the outer subventricular zone of the primate. Neuron 80 (2013), 442–457.
Shitamukai, A., Konno, D., Matsuzaki, F., Oblique radial glial divisions in the developing mouse neocortex induce self-renewing progenitors outside the germinal zone that resemble primate outer subventricular zone progenitors. J Neurosci 31 (2011), 3683–3695.
Wang, X., Tsai, J.W., LaMonica, B., Kriegstein, A.R., A new subtype of progenitor cell in the mouse embryonic neocortex. Nat Neurosci 14 (2011), 555–561.
Fietz, S.A., Kelava, I., Vogt, J., Wilsch-Bräuninger, M., Stenzel, D., Fish, J.L., Corbeil, D., Riehn, A., Distler, W., Nitsch, R., et al. OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling. Nat Neurosci 13 (2010), 690–699.
Reillo, I., de Juan Romero, C., Garcia-Cabezas, M.A., Borrell V: a role for intermediate radial glia in the tangential expansion of the mammalian cerebral cortex. Cerebr Cortex 21 (2011), 1674–1694.
Borrell, V., Götz, M., Role of radial glial cells in cerebral cortex folding. Curr Opin Neurobiol 27 (2014), 39–46.
Smart, I.H., Dehay, C., Giroud, P., Berland, M., Kennedy, H., Unique morphological features of the proliferative zones and postmitotic compartments of the neural epithelium giving rise to striate and extrastriate cortex in the monkey. Cerebr Cortex 12 (2002), 37–53.
Reillo, I., Borrell, V., Germinal zones in the developing cerebral cortex of ferret: ontogeny, cell cycle kinetics, and diversity of progenitors. Cerebr Cortex 22 (2012), 2039–2054.
Dehay, C., Kennedy, H., Kosik, K.S., The outer subventricular zone and primate-specific cortical complexification. Neuron 85 (2015), 683–694.
Herculano-Houzel, S., Collins, C.E., Wong, P., Kaas, J.H., Cellular scaling rules for primate brains. Proc Natl Acad Sci USA 104 (2007), 3562–3567.
Donahue, C.J., Glasser, M.F., Preuss, T.M., Rilling, J.K., Van Essen, D.C., Quantitative assessment of prefrontal cortex in humans relative to nonhuman primates. Proc Natl Acad Sci U S A 115 (2018), 5183–5192.
Florio, M., Heide, M., Pinson, A., Brandl, H., Albert, M., Winkler, S., Wimberger, P., Huttner, W.B., Hiller, M., Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex. eLife, 7, 2018, e32332.
Sudmant, P.H., Kitzman, J.O., Antonacci, F., Alkan, C., Malig, M., Tsalenko, A., Sampas, N., Bruhn, L., Shendure, J., Genomes, P., et al. Diversity of human copy number variation and multicopy genes. Science 330 (2010), 641–646.
Antonacci, F., Dennis, M.Y., Huddleston, J., Sudmant, P.H., Steinberg, K.M., Rosenfeld, J.A., Miroballo, M., Graves, T.A., Vives, L., Malig, M., et al. Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability. Nat Genet 46 (2014), 1293–1302.
Florio, M., Namba, T., Pääbo, S., Hiller, M., Huttner, W.B., A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification. Sci Adv, 2, 2016, e1601941.
Florio, M., Albert, M., Taverna, E., Namba, T., Brandl, H., Lewitus, E., Haffner, C., Sykes, A., Wong, F.K., Peters, J., et al. Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion. Science 347 (2015), 1465–1470.
Namba, T., Doczi, J., Pinson, A., Xing, L., Kalebic, N., Wilsch-Brauninger, M., Long, K.R., Vaid, S., Lauer, J., Bogdanova, A., et al. Human-specific ARHGAP11B acts in mitochondria to expand neocortical progenitors by glutaminolysis. Neuron 105 (2020), 867–881 This study reports that the ARHGAP11B protein is localized in mitochondria where it interacts with the adenine nucleotide translocase and inhibits the mitochondrial permeability transition pore. This inhibition leads to an increase in mitochondrial calcium concentration and promotes glutaminolysis, which is required to sustain the full level of human BP proliferation.
Kalebic, N., Gilardi, C., Albert, M., Namba, T., Long, K.R., Kostic, M., Langen, B., Huttner, W.B., Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex. eLife, 7, 2018, e41241.
Heide, M., Haffner, C., Murayama, A., Kurotaki, Y., Shinohara, H., Okano, H., Sasaki, E., Huttner, W.B., Human-specific ARHGAP11B increases size and folding of primate neocortex in the fetal marmoset. Science 369 (2020), 546–550 This study describes the effects of physiologically relevant ARHGAP11B expression in the neocortex of transgenic fetuses of the common marmoset. ARHGAP11B increases the number of bRG in the oSVZ, increases specifically the number of upper-layer neurons, enlarges the neocortex and induces folding of this otherwise lissencephalic fetal neocortex.
Yang, L., Venneti, S., Nagrath, D., Glutaminolysis: a hallmark of cancer metabolism. Annu Rev Biomed Eng 19 (2017), 163–194.
Namba, T., Nardelli, J., Gressens, P., Huttner, W.B., Metabolic regulation of neocortical expansion in development and evolution. Neuron 109 (2021), 408–419.
Journiac, N., Gilabert-Juan, J., Cipriani, S., Benit, P., Liu, X., Jacquier, S., Faivre, V., Delahaye-Duriez, A., Csaba, Z., Hourcade, T., et al. Cell metabolic alterations due to Mcph1 mutation in microcephaly. Cell Rep, 31, 2020, 107506 This paper reveals that the protein encoded by a gene implicated in primary microcephaly, Mcph1, is localized in association with mitochondria in the mouse embryonic neocortex and stimulates aRG proliferation via glutaminolysis.
Iwata, R., Casimir, P., Vanderhaeghen, P., Mitochondrial dynamics in postmitotic cells regulate neurogenesis. Science 369 (2020), 858–862 The study reveals that mitochondrial dynamics shortly after NPC mitosis are important to determine the fate of the daughter cells. The induction of mitochondrial fusion after mitosis directs the daughter cells toward self-renewal, whereas the induction of fission promotes neuronal fate.
Brunetti-Pierri, N., Berg, J.S., Scaglia, F., Belmont, J., Bacino, C.A., Sahoo, T., Lalani, S.R., Graham, B., Lee, B., Shinawi, M., et al. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities. Nat Genet 40 (2008), 1466–1471.
Fiddes, I.T., Lodewijk, G.A., Mooring, M., Bosworth, C.M., Ewing, A.D., Mantalas, G.L., Novak, A.M., van den Bout, A., Bishara, A., Rosenkrantz, J.L., et al. Human-specific NOTCH2NL genes affect notch signaling and cortical neurogenesis. Cell 173 (2018), 1356–1369.
Lodewijk, G.A., Fernandes, D.P., Vretzakis, I., Savage, J.E., Jacobs, F.M.J., Evolution of human brain size-associated NOTCH2NL genes proceeds toward reduced protein levels. Mol Biol Evol 37 (2020), 2531–2548.
Suzuki, I.K., Gacquer, D., Van Heurck, R., Kumar, D., Wojno, M., Bilheu, A., Herpoel, A., Lambert, N., Cheron, J., Polleux, F., et al. Human-specific NOTCH2NL genes expand cortical neurogenesis through Delta/Notch regulation. Cell 173 (2018), 1370–1384.
Funato, K., Smith, R.C., Saito, Y., Tabar, V., Dissecting the impact of regional identity and the oncogenic role of human-specific NOTCH2NL in an hESC model of H3.3G34R-mutant glioma. Cell Stem Cell, 2021, 10.1016/j.stem.2021.1002.1003 Using a human embryonic stem cell-based model of H3.3G34R mutant glioma, the authors report that the expression of the human-specific gene NOTCH2NL is increased in the mutant compared to the wildtype cells. This study is the first published link between the expression of a human-specific gene expressed in fetal human neocortex and the proliferation of glioma cells.
Bhaduri, A., Di Lullo, E., Jung, D., Müller, S., Crouch, E.E., Espinosa, C.S., Ozawa, T., Alvarado, B., Spatazza, J., Cadwell, C.R., et al. Outer radial glia-like cancer stem cells contribute to heterogeneity of glioblastoma. Cell Stem Cell 26 (2020), 48–63 The authors use single-cell RNA sequencing of primary glioblastoma tumors in order to generate an atlas of gene expression. They identify a population of glioblastoma cells that correspond to bRG, a cell type implicated in neocortex expansion. The tumor-derived bRG-like cells are implicated in glioblastoma tumor invasion.
Wang, R., Sharma, R., Shen, X., Laughney, A.M., Funato, K., Clark, P.J., Shpokayte, M., Morgenstern, P., Navare, M., Xu, Y., et al. Adult human glioblastomas harbor radial glia-like cells. Stem Cell Rep 14 (2020), 338–350.
Ju, X.C., Hou, Q.Q., Sheng, A.L., Wu, K.Y., Zhou, Y., Jin, Y., Wen, T., Yang, Z., Wang, X., Luo, Z.G., The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice. Elife, 5, 2016, e18197.
Liu, J., Liu, W., Yang, L., Wu, Q., Zhang, H., Fang, A., Li, L., Xu, X., Sun, L., Zhang, J., et al. The primate-specific gene TMEM14B marks outer radial glia cells and promotes cortical expansion and folding. Cell Stem Cell 21 (2017), 635–649.
Fietz, S.A., Lachmann, R., Brandl, H., Kircher, M., Samusik, N., Schroder, R., Lakshmanaperumal, N., Henry, I., Vogt, J., Riehn, A., 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 USA 109 (2012), 11836–11841.
Johnson, M.B., Wang, P.P., Atabay, K.D., Murphy, E.A., Doan, R.N., Hecht, J.L., Walsh, C.A., Single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex. Nat Neurosci 18 (2015), 637–646.
Pollen, A.A., Nowakowski, T.J., Chen, J., Retallack, H., Sandoval-Espinosa, C., Nicholas, C.R., Shuga, J., Liu, S.J., Oldham, M.C., Diaz, A., et al. Molecular identity of human outer radial glia during cortical development. Cell 163 (2015), 55–67.
Miller, J.A., Ding, S.L., Sunkin, S.M., Smith, K.A., Ng, L., Szafer, A., Ebbert, A., Riley, Z.L., Royall, J.J., Aiona, K., et al. Transcriptional landscape of the prenatal human brain. Nature 508 (2014), 199–206.
Stahl, R., Walcher, T., De Juan Romero, C., Pilz, G.A., Cappello, S., Irmler, M., Sanz-Aquela, J.M., Beckers, J., Blum, R., Borrell, V., et al. Trnp1 regulates expansion and folding of the mammalian cerebral cortex by control of radial glial fate. Cell 153 (2013), 535–549.
Lui, J.H., Nowakowski, T.J., Pollen, A.A., Javaherian, A., Kriegstein, A.R., Oldham, M.C., Radial glia require PDGFD-PDGFRbeta signalling in human but not mouse neocortex. Nature 515 (2014), 264–268.
Kostic, M., Paridaen, J., Long, K.R., Kalebic, N., Langen, B., Grubling, N., Wimberger, P., Kawasaki, H., Namba, T., Huttner, W.B., YAP activity is aecessary and sufficient for basal progenitor abundance and proliferation in the developing neocortex. Cell Rep 27 (2019), 1103–1118.
Nowakowski, T.J., Pollen, A.A., Sandoval-Espinosa, C., Kriegstein, A.R., Transformation of the radial glia scaffold demarcates two stages of human cerebral cortex development. Neuron 91 (2016), 1219–1227.
Thomsen, E.R., Mich, J.K., Yao, Z., Hodge, R.D., Doyle, A.M., Jang, S., Shehata, S.I., Nelson, A.M., Shapovalova, N.V., Levi, B.P., et al. Fixed single-cell transcriptomic characterization of human radial glial diversity. Nat Methods 13 (2016), 87–93.
Vaid, S., Camp, J.G., Hersemann, L., Eugster Oegema, C., Heninger, A.K., Winkler, S., Brandl, H., Sarov, M., Treutlein, B., Huttner, W.B., et al. A novel population of Hopx-dependent basal radial glial cells in the developing mouse neocortex. Development, 145, 2018 dev169276.
Zweifel, S., Marcy, G., Lo Guidice Q, Li D, Heinrich C, Azim K, Raineteau O: HOPX defines heterogeneity of postnatal subventricular zone neural stem cells. Stem Cell Rep 11 (2018), 770–783.
Matsumoto, N., Tanaka, S., Horiike, T., Shinmyo, Y., Kawasaki, H., A discrete subtype of neural progenitor crucial for cortical folding in the gyrencephalic mammalian brain. Elife, 9, 2020, e54873 This study shows that bRG in the developing ferret neocortex fall into two populations, Hopx-positive and Hopx-negative bRG. Hopx-positive bRG correspond to proliferative bRG and are regulated by Shh signaling. The suppression of Shh signaling using in utero electroporation reduces the number of Hopx-positive bRG. Conversely, the stimulation of Shh signaling increases the number of Hopx-positive bRG.
Stenzel, D., Wilsch-Bräuninger, M., Wong, F.K., Heuer, H., Huttner, W.B., Integrin αvß3 and thyroid hormones promote expansion of progenitors in embryonic neocortex. Development 141 (2014), 795–806.
Güven, A., Kalebic, N., Long, K.R., Florio, M., Vaid, S., Brandl, H., Stenzel, D., Huttner, W.B., Extracellular matrix-inducing Sox9 promotes both basal progenitor proliferation and gliogenesis in developing neocortex. Elife, 9, 2020, e49808 The authors report that the transcription factor Sox9 induces the expression of extracellular matrix components and hence may have played a role in neocortical expansion. Conditional Sox9 expression in the mouse BP lineage, which normally does not express Sox9, increases BP proliferation and induces premature gliogenesis. In addition, Sox9 expression leads to a non-cell-autonomous increase in BP proliferation and upper-layer neuron production.
Mayer, S., Chen, J., Velmeshev, D., Mayer, A., Eze, U.C., Bhaduri, A., Cunha, C.E., Jung, D., Arjun, A., Li, E., et al. Multimodal single-cell analysis reveals physiological maturation in the developing human neocortex. Neuron 102 (2019), 143–158 The authors developed a microfluidic-like approach to link calcium imaging in response to agonists of different neurotransmitter receptors with single-cell RNA sequencing of fetal human neocortex tissue. The serotonin receptor HTR2A is found to be expressed in fetal human neocortex VZ and SVZ but not in embryonic mouse neocortex. An HTR2A agonist induced calcium signaling in radial glia of fetal human, but not in embryonic mouse, neocortex. An inhibition of HTR2A receptor in fetal human neocortex disrupts the radial glia scaffold.
Xing, L., Kalebic, N., Namba, T., Vaid, S., Wimberger, P., Huttner, W.B., Serotonin receptor 2A activation promotes evolutionarily relevant basal progenitor proliferation in the developing neocortex. Neuron 108 (2020), 1113–1129 This study reports that the serotonin receptor HTR2A, which is expressed in the developing ferret and human neocortex but not in the developing mouse neocortex, is required and sufficient to increase BP proliferation. HTR2A activation increases proliferative BPs at the expense of neurogenic BPs through HER2 and ERK1/2 signaling, an increase that may have contributed to the evolutionary expansion of the neocortex.
Kalebic, N., Gilardi, C., Stepien, B., Wilsch-Bräuninger, M., Long, K.R., Namba, T., Florio, M., Langen, B., Lombardot, B., Shevchenko, A., et al. Neocortical expansion due to increased proliferation of basal progenitors is linked to changes in their morphology. Cell Stem Cell 24 (2019), 535–550 This study reveals that the increased proliferative capacity of BPs in species with an expanded neocortex correlates with an increase in the number of BP processes. The expression of the membrane-bound form of PALMD increases the number of BP processes, resulting in activation of integrin signaling, which in turn leads to enhanced BP proliferation.
Reillo, I., de Juan Romero, C., Cardenas, A., Clasca, F., Martinez-Martinez, M.A., Borrell V: a complex code of extrinsic influences on cortical progenitor cells of higher mammals. Cerebr Cortex 27 (2017), 4586–4606.
Kalebic, N., Huttner, W.B., Basal progenitor morphology and neocortex evolution. Trends Neurosci 43 (2020), 843–853.
Mora-Bermudez, F., Badsha, F., Kanton, S., Camp, J.G., Vernot, B., Kohler, K., Voigt, B., Okita, K., Maricic, T., He, Z., et al. Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development. eLife, 5, 2016, e18683.
Kanton, S., Boyle, M.J., He, Z.S., Santel, M., Weigert, A., Sanchis-Calleja, F., Guijarro, P., Sidow, L., Fleck, J.S., Han, D.D., et al. Organoid single-cell genomic atlas uncovers human-specific features of brain development. Nature 574 (2019), 418–422 By making use of single-cell transcriptomic and accessible chromatin profiling of human, chimpanzee and macaque cerebral organoids, the authors associate divergence in chromatin accessibility with human-specific gene expression changes. They report a slower neuronal development in human cerebral organoids than in chimpanzee and macaque cerebral organoids.
Pollen, A.A., Bhaduri, A., Andrews, M.G., Nowakowski, T.J., Meyerson, O.S., Mostajo-Radji, M.A., Di Lullo, E., Alvarado, B., Bedolli, M., Dougherty, M.L., et al. Establishing cerebral organoids as models of human-specific brain evolution. Cell 176 (2019), 743–756 Using single-cell RNA sequencing, the authors identify 261 genes differentially expressed between human and macaque primary cortical cells as well as between human and chimpanzee organoid cells. Among these genes, INSR and ITGB8 are preferentially expressed in human bRG compared to chimpanzee and macaque bRG and shown to promote the activation of the PI3K-AKT-mTOR pathway in human oSVZ.
Benito-Kwiecinski, S., Giandomenico, S.L., Sutcliffe, M., Riis, E.S., Freire-Pritchett, P., Kelava, I., Wunderlich, S., Martin, U., Wray, G.A., McDole, K., et al. An early cell shape transition drives evolutionary expansion of the human forebrain. Cell, 2021, 10.1016/j.cell.2021.1002.1050 Taking advantage of cerebral organoids, this study reports that the transformation of neuroepithelial cells to aRG is protracted in gorilla compared to human. The authors show through loss- and gain-of-function experiments that the transcription factor ZEB2 promotes this transformation. The ectopic expression of ZEB2 in human cerebral organoids is sufficient to trigger a premature transformation of neuroepithelial cells to aRG.
Otani, T., Marchetto, M.C., Gage, F.H., Simons, B.D., Livesey, F.J., 2D and 3D stem cell models of primate cortical development identify species-specific differences in progenitor behavior contributing to brain size. Cell Stem Cell 18 (2016), 467–480.
Marchetto, M.C., Hrvoj-Mihic, B., Kerman, B.E., Yu, D.X., Vadodaria, K.C., Linker, S.B., Narvaiza, I., Santos, R., Denli, A.M., Mendes, A.P., et al. Species-specific maturation profiles of human, chimpanzee and bonobo neural cells. Elife, 8, 2019, e37527 Using the induced pluripotent stem cell technology to model human, chimpanzee and bonobo neurons, the authors found that chimpanzee and bonobo neurons migrate faster and further than human neurons, in vitro and in vivo upon transplantation into postnatal mouse brain. Moreover, the dendritic arborization develops faster in chimpanzee than in human neurons, which was corroborated by functional studies using a multi-well microelectrode array platform.
Schörnig, M., Ju, X., Fast, L., Ebert, S., Weigert, A., Kanton, S., Schaffer, T., Nadif Kasri, N., Treutlein, B., Peter, B.M., et al. Comparison of induced neurons reveals slower structural and functional maturation in humans than in apes. Elife, 10, 2021, e59323 The authors generated induced chimpanzee, bonobo and human excitatory neurons from stem cells by expressing the transcription factor neurogenin-2. Single-cell RNA sequencing as well as morphological and functional analyses reveal that chimpanzee and bonobo induced neurons mature faster than human induced neurons.
Guerrier, S., Coutinho-Budd, J., Sassa, T., Gresset, A., Jordan, N.V., Chen, K., Jin, W.L., Frost, A., Polleux, F., The F-BAR domain of srGAP2 induces membrane protrusions required for neuronal migration and morphogenesis. Cell 138 (2009), 990–1004.
Schmidt, E.R.E., Kupferman, J.V., Stackmann, M., Polleux, F., The human-specific paralogs SRGAP2B and SRGAP2C differentially modulate SRGAP2A-dependent synaptic development. Sci Rep, 9, 2019, 18692.
Charrier, C., Joshi, K., Coutinho-Budd, J., Kim, J.E., Lambert, N., de Marchena, J., Jin, W.L., Vanderhaeghen, P., Ghosh, A., Sassa, T., et al. Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation. Cell 149 (2012), 923–935.
Fossati, M., Pizzarelli, R., Schmidt, E.R., Kupferman, J.V., Stroebel, D., Polleux, F., Charrier, C., SRGAP2 and its human-specific paralog co-regulate the development of excitatory and inhibitory synapses. Neuron 91 (2016), 356–369.
Trujillo, C.A., Rice, E.S., Schaefer, N.K., Chaim, I.A., Wheeler, E.C., Madrigal, A.A., Buchanan, J., Preissl, S., Wang, A., Negraes, P.D., et al. Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment. Science, 371, 2021 eaax2537 This study addresses a single-nucleotide substitution that results in an isoleucine-to-valine change in the RNA-binding protein NOVA1 in modern human compared to Neanderthals and Denisovans. Cortical organoids grown from induced pluripotent stem cells edited to re-introduce the archaic allele of NOVA1 display lower levels of synaptic proteins and alteration of glutamatergic signaling.