Abstract
During central nervous system (CNS) development, neural progenitor cells (NPCs) generate neurons and glia in two different ways. In direct neurogenesis, daughter cells differentiate directly into neurons or glia, whereas in indirect neurogenesis, neurons or glia are generated after one or more daughter cell divisions. Intriguingly, indirect neurogenesis is not stochastically deployed and plays instructive roles during CNS development: increased generation of cells from specific lineages; increased generation of early or late-born cell types within a lineage; and increased cell diversification. Increased indirect neurogenesis might contribute to the anterior CNS expansion evident throughout the Bilateria and help to modify brain-region size without requiring increased NPC numbers or extended neurogenesis. Increased indirect neurogenesis could be an evolutionary driver of the gyrencephalic (that is, folded) cortex that emerged during mammalian evolution and might even have increased during hominid evolution. Thus, selection of indirect versus direct neurogenesis provides a powerful developmental and evolutionary instrument that drives not only the evolution of CNS complexity but also brain expansion and modulation of brain-region size, and thereby the evolution of increasingly advanced cognitive abilities. This Review describes indirect neurogenesis in several model species and humans, and highlights some of the molecular genetic mechanisms that control this important process.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Allan, D. W. & Thor, S. Transcriptional selectors, masters, and combinatorial codes: regulatory principles of neural subtype specification. Wiley Interdiscip. Rev. Dev. Biol. 4, 505–528 (2015).
Arendt, D. & Nubler-Jung, K. Comparison of early nerve cord development in insects and vertebrates. Development 126, 2309–2325 (1999).
Cadwell, C. R., Bhaduri, A., Mostajo-Radji, M. A., Keefe, M. G. & Nowakowski, T. J. Development and arealization of the cerebral cortex. Neuron 103, 980–1004 (2019).
Lumsden, A. & Krumlauf, R. Patterning the vertebrate neuraxis. Science 274, 1109–1115 (1996).
Doe, C. Q. Temporal patterning in the Drosophila CNS. Annu. Rev. Cell Dev. Biol. 33, 219–240 (2017).
El-Danaf, R. N., Rajesh, R. & Desplan, C. Temporal regulation of neural diversity in Drosophila and vertebrates. Semin. Cell Dev. Biol. 142, 13–22 (2023).
Oberst, P., Agirman, G. & Jabaudon, D. Principles of progenitor temporal patterning in the developing invertebrate and vertebrate nervous system. Curr. Opin. Neurobiol. 56, 185–193 (2019).
Santos-Franca, P. L., David, L. A., Kassem, F., Meng, X. Q. & Cayouette, M. Time to see: how temporal identity factors specify the developing mammalian retina. Semin. Cell Dev. Biol. 142, 36–42 (2023).
Casas Gimeno, G. & Paridaen, J. The symmetry of neural stem cell and progenitor divisions in the vertebrate brain. Front. Cell Dev. Biol. 10, 885269 (2022).
Sousa-Nunes, R. & Somers, W. G. Mechanisms of asymmetric progenitor divisions in the Drosophila central nervous system. Adv. Exp. Med. Biol. 786, 79–102 (2013).
Espinos, A., Fernandez-Ortuno, E., Negri, E. & Borrell, V. Evolution of genetic mechanisms regulating cortical neurogenesis. Dev. Neurobiol. 82, 428–453 (2022).
Kalebic, N. & Huttner, W. B. Basal progenitor morphology and neocortex evolution. Trends Neurosci. 43, 843–853 (2020).
Kriegstein, A., Noctor, S. & Martinez-Cerdeno, V. Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion. Nat. Rev. Neurosci. 7, 883–890 (2006).
Del-Valle-Anton, L. et al. Multiple parallel cell lineages in the developing mammalian cerebral cortex. Sci. Adv. 10, eadn9998 (2024).
Monedero Cobeta, I., Salmani, B. Y. & Thor, S. Anterior–posterior gradient in neural stem and daughter cell proliferation governed by spatial and temporal Hox control. Curr. Biol. 27, 1161–1172 (2017).
Ulvklo, C. et al. Control of neuronal cell fate and number by integration of distinct daughter cell proliferation modes with temporal progression. Development 139, 678–689 (2012).
Cardenas, A. & Borrell, V. Molecular and cellular evolution of corticogenesis in amniotes. Cell Mol. Life Sci. 77, 1435–1460 (2020).
Huilgol, D. et al. Direct and indirect neurogenesis generate a mosaic of distinct glutamatergic projection neuron types in cerebral cortex. Neuron 111, 2557–2569.e4 (2023).
Huilgol, D., Russ, J. B., Srivas, S. & Huang, Z. J. The progenitor basis of cortical projection neuron diversity. Curr. Opin. Neurobiol. 81, 102726 (2023).
Suryanarayana, S. M. & Huilgol, D. Conservation and diversification of pallial cell types across vertebrates: an evo-devo perspective. Brain Behav. Evol. 98, 210–228 (2023).
Yaghmaeian Salmani, B. & Thor, S. Genetic mechanisms controlling anterior expansion of the central nervous system. Curr. Top. Dev. Biol. 137, 333–361 (2020).
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. USA 101, 3196–3201 (2004).
McIntosh, R., Norris, J., Clarke, J. D. & Alexandre, P. Spatial distribution and characterization of non-apical progenitors in the zebrafish embryo central nervous system. Open Biol. 7, 160312 (2017).
Smart, I. H. Proliferative characteristics of the ependymal layer during the early development of the mouse diencephalon, as revealed by recording the number, location, and plane of cleavage of mitotic figures. J. Anat. 113, 109–129 (1972).
Pinson, A. et al. Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals. Science 377, eabl6422 (2022).
Ostrem, B., Di Lullo, E. & Kriegstein, A. oRGs and mitotic somal translocation — a role in development and disease. Curr. Opin. Neurobiol. 42, 61–67 (2017).
Denoth-Lippuner, A. & Jessberger, S. Formation and integration of new neurons in the adult hippocampus. Nat. Rev. Neurosci. 22, 223–236 (2021).
Jurkowski, M. P. et al. Beyond the hippocampus and the SVZ: adult neurogenesis throughout the brain. Front. Cell Neurosci. 14, 576444 (2020).
Obernier, K. & Alvarez-Buylla, A. Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain. Development 146, dev156059 (2019).
Adameyko, I. Evolutionary origin of the neural tube in basal deuterostomes. Curr. Biol. 33, R319–R331 (2023).
Arendt, D., Tosches, M. A. & Marlow, H. From nerve net to nerve ring, nerve cord and brain—evolution of the nervous system. Nat. Rev. Neurosci. 17, 61–72 (2016).
Northcutt, R. G. Understanding vertebrate brain evolution. Integr. Comp. Biol. 42, 743–756 (2002).
Birkholz, O., Rickert, C., Berger, C., Urbach, R. & Technau, G. M. Neuroblast pattern and identity in the Drosophila tail region and role of doublesex in the survival of sex-specific precursors. Development 140, 1830–1842 (2013).
Bossing, T., Udolph, G., Doe, C. Q. & Technau, G. M. The embryonic central nervous system lineages of Drosophila melanogaster. I. Neuroblast lineages derived from the ventral half of the neuroectoderm. Dev. Biol. 179, 41–64 (1996).
Schmid, A., Chiba, A. & Doe, C. Q. Clonal analysis of Drosophila embryonic neuroblasts: neural cell types, axon projections and muscle targets. Development 126, 4653–4689 (1999).
Schmidt, H. et al. The embryonic central nervous system lineages of Drosophila melanogaster. II. Neuroblast lineages derived from the dorsal part of the neuroectoderm. Dev. Biol. 189, 186–204 (1997).
Wheeler, S. R., Stagg, S. B. & Crews, S. T. MidExDB: a database of Drosophila CNS midline cell gene expression. BMC Dev. Biol. 9, 56 (2009).
Urbach, R., Schnabel, R. & Technau, G. M. The pattern of neuroblast formation, mitotic domains and proneural gene expression during early brain development in Drosophila. Development 130, 3589–3606 (2003).
Younossi-Hartenstein, A., Nassif, C., Green, P. & Hartenstein, V. Early neurogenesis of the Drosophila brain. J. Comp. Neurol. 370, 313–329 (1996).
Urbach, R., Jussen, D. & Technau, G. M. Gene expression profiles uncover individual identities of gnathal neuroblasts and serial homologies in the embryonic CNS of Drosophila. Development 143, 1290–1301 (2016).
Doe, C. Q. Neural stem cells: balancing self-renewal with differentiation. Development 135, 1575–1587 (2008).
Knoblich, J. A. Asymmetric cell division: recent developments and their implications for tumour biology. Nat. Rev. Mol. Cell Biol. 11, 849–860 (2010).
Rogulja-Ortmann, A., Luer, K., Seibert, J., Rickert, C. & Technau, G. M. Programmed cell death in the embryonic central nervous system of Drosophila melanogaster. Development 134, 105–116 (2007).
Boone, J. Q. & Doe, C. Q. Identification of Drosophila type II neuroblast lineages containing transit amplifying ganglion mother cells. Dev. Neurobiol. 68, 1185–1195 (2008).
Bello, B. C., Izergina, N., Caussinus, E. & Reichert, H. Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development. Neural Dev. 3, 5 (2008).
Bowman, S. K. et al. The tumor suppressors Brat and Numb regulate transit-amplifying neuroblast lineages in Drosophila. Dev. Cell 14, 535–546 (2008).
Alvarez, J. A. & Diaz-Benjumea, F. J. Origin and specification of type II neuroblasts in the Drosophila embryo. Development 145, dev158394 (2018).
Walsh, K. T. & Doe, C. Q. Drosophila embryonic type II neuroblasts: origin, temporal patterning, and contribution to the adult central complex. Development 144, 4552–4562 (2017).
Baumgardt, M., Karlsson, D., Terriente, J., Diaz-Benjumea, F. J. & Thor, S. Neuronal subtype specification within a lineage by opposing temporal feed-forward loops. Cell 139, 969–982 (2009).
Karcavich, R. & Doe, C. Q. Drosophila neuroblast 7-3 cell lineage: a model system for studying programmed cell death, Notch/Numb signaling, and sequential specification of ganglion mother cell identity. J. Comp. Neurol. 481, 240–251 (2005).
Baumgardt, M. et al. Global programmed switch in neural daughter cell proliferation mode triggered by a temporal gene cascade. Dev. Cell 30, 192–208 (2014).
Bertet, C. et al. Temporal patterning of neuroblasts controls Notch-mediated cell survival through regulation of Hid or Reaper. Cell 158, 1173–1186 (2014).
Bahrampour, S., Jonsson, C. & Thor, S. Brain expansion promoted by Polycomb-mediated anterior enhancement of a neural stem cell proliferation program. PLoS Biol. 17, e3000163 (2019).
Yaghmaeian Salmani, B. et al. Evolutionarily conserved anterior expansion of the central nervous system promoted by a common PcG–Hox program. Development 145, dev160747 (2018).
Choksi, S. P. et al. Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells. Dev. Cell 11, 775–789 (2006).
Li, L. & Vaessin, H. Pan-neural Prospero terminates cell proliferation during Drosophila neurogenesis. Genes. Dev. 14, 147–151 (2000).
Pollington, H. Q., Seroka, A. Q. & Doe, C. Q. From temporal patterning to neuronal connectivity in Drosophila type I neuroblast lineages. Semin. Cell Dev. Biol. 142, 4–12 (2023).
Bahrampour, S., Gunnar, E., Jonsson, C., Ekman, H. & Thor, S. Neural lineage progression controlled by a temporal proliferation program. Dev. Cell 43, 332–348.e4 (2017).
Bivik, C. et al. Control of neural daughter cell proliferation by multi-level Notch/Su(H)/E(spl)-HLH signaling. PLoS Genet. 12, e1005984 (2016).
Guillamon-Vivancos, T. et al. Distinct neocortical progenitor lineages fine-tune neuronal diversity in a layer-specific manner. Cereb. Cortex 29, 1121–1138 (2019).
Li, Z. et al. Transcriptional priming as a conserved mechanism of lineage diversification in the developing mouse and human neocortex. Sci. Adv. 6, eabd2068 (2020).
Tyler, W. A., Medalla, M., Guillamon-Vivancos, T., Luebke, J. I. & Haydar, T. F. Neural precursor lineages specify distinct neocortical pyramidal neuron types. J. Neurosci. 35, 6142–6152 (2015).
Curt, J. R., Yaghmaeian Salmani, B. & Thor, S. Anterior CNS expansion driven by brain transcription factors. eLife 8, e45274 (2019).
Younossi-Hartenstein, A. et al. Control of early neurogenesis of the Drosophila brain by the head gap genes tll, otd, ems, and btd. Dev. Biol. 182, 270–283 (1997).
Hirth, F., Hartmann, B. & Reichert, H. Homeotic gene action in embryonic brain development of Drosophila. Development 125, 1579–1589 (1998).
Philippidou, P. & Dasen, J. S. Hox genes: choreographers in neural development, architects of circuit organization. Neuron 80, 12–34 (2013).
Karlsson, D., Baumgardt, M. & Thor, S. Segment-specific neuronal subtype specification by the integration of anteroposterior and temporal cues. PLoS Biol. 8, e1000368 (2010).
Rogulja-Ortmann, A. et al. The RNA-binding protein ELAV regulates Hox RNA processing, expression and function within the Drosophila nervous system. Development 141, 2046–2056 (2014).
Tycko, J. et al. High-throughput discovery and characterization of human transcriptional effectors. Cell 183, 2020–2035.e16 (2020).
Holland, P. W. Evolution of homeobox genes. Wiley Interdiscip. Rev. Dev. Biol. 2, 31–45 (2013).
Muller, J. & Verrijzer, P. Biochemical mechanisms of gene regulation by Polycomb group protein complexes. Curr. Opin. Genet. Dev. 19, 150–158 (2009).
Rajan, A., Ostgaard, C. M. & Lee, C. Y. Regulation of neural stem cell competency and commitment during indirect neurogenesis. Int. J. Mol. Sci. 22, 12871 (2021).
Haenfler, J. M., Kuang, C. & Lee, C. Y. Cortical aPKC kinase activity distinguishes neural stem cells from progenitor cells by ensuring asymmetric segregation of Numb. Dev. Biol. 365, 219–228 (2012).
Komori, H., Golden, K. L., Kobayashi, T., Kageyama, R. & Lee, C. Y. Multilayered gene control drives timely exit from the stem cell state in uncommitted progenitors during Drosophila asymmetric neural stem cell division. Genes. Dev. 32, 1550–1561 (2018).
Reichardt, I. et al. The tumor suppressor Brat controls neuronal stem cell lineages by inhibiting Deadpan and Zelda. EMBO Rep. 19, 102–117 (2018).
Berger, C. et al. FACS purification and transcriptome analysis of Drosophila neural stem cells reveals a role for Klumpfuss in self-renewal. Cell Rep. 2, 407–418 (2012).
Janssens, D. H. et al. An Hdac1/Rpd3-poised circuit balances continual self-renewal and rapid restriction of developmental potential during asymmetric stem cell division. Dev. Cell 40, 367–380.e7 (2017).
Janssens, D. H. et al. Earmuff restricts progenitor cell potential by attenuating the competence to respond to self-renewal factors. Development 141, 1036–1046 (2014).
San-Juan, B. P. & Baonza, A. The bHLH factor deadpan is a direct target of Notch signaling and regulates neuroblast self-renewal in Drosophila. Dev. Biol. 352, 70–82 (2011).
Xiao, Q., Komori, H. & Lee, C.-Y. klumpfuss distinguishes stem cells from progenitor cells during asymmetric neuroblast division. Development 139, 2670–2680 (2012).
Zacharioudaki, E. et al. Genes implicated in stem cell identity and temporal programme are directly targeted by Notch in neuroblast tumours. Development 143, 219–231 (2016).
Zacharioudaki, E., Magadi, S. S. & Delidakis, C. bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and mediate Notch-induced overproliferation. Development 139, 1258–1269 (2012).
Zhu, S. et al. The bHLH repressor Deadpan regulates the self-renewal and specification of Drosophila larval neural stem cells independently of Notch. PLoS ONE 7, e46724 (2012).
Hakes, A. E. & Brand, A. H. Tailless/TLX reverts intermediate neural progenitors to stem cells driving tumourigenesis via repression of asense/ASCL1. eLife 9, e53377 (2020).
Rives-Quinto, N. et al. Sequential activation of transcriptional repressors promotes progenitor commitment by silencing stem cell identity genes. eLife 9, e56187 (2020).
Xie, Y. et al. The Ets protein Pointed prevents both premature differentiation and dedifferentiation of Drosophila intermediate neural progenitors. Development 143, 3109–3118 (2016).
Xie, Y. et al. The Drosophila Sp8 transcription factor Buttonhead prevents premature differentiation of intermediate neural progenitors. eLife 3, e03596 (2014).
Zhu, S., Barshow, S., Wildonger, J., Jan, L. Y. & Jan, Y. N. Ets transcription factor Pointed promotes the generation of intermediate neural progenitors in Drosophila larval brains. Proc. Natl Acad. Sci. USA 108, 20615–20620 (2011).
Weng, M., Golden, K. L. & Lee, C. Y. dFezf/Earmuff maintains the restricted developmental potential of intermediate neural progenitors in Drosophila. Dev. Cell 18, 126–135 (2010).
Koe, C. T. et al. The Brm-HDAC3-Erm repressor complex suppresses dedifferentiation in Drosophila type II neuroblast lineages. eLife 3, e01906 (2014).
Zhang, Y. et al. The Integrator complex prevents dedifferentiation of intermediate neural progenitors back into neural stem cells. Cell Rep. 27, 987–996.e3 (2019).
Bayraktar, O. A. & Doe, C. Q. Combinatorial temporal patterning in progenitors expands neural diversity. Nature 498, 449–455 (2013).
Thor, S. Neuroscience: stem cells in multiple time zones. Nature 498, 441–443 (2013).
Farnsworth, D. R., Bayraktar, O. A. & Doe, C. Q. Aging neural progenitors lose competence to respond to mitogenic Notch signaling. Curr. Biol. 25, 3058–3068 (2015).
Lacin, H., Zhu, Y., Wilson, B. A. & Skeath, J. B. Transcription factor expression uniquely identifies most postembryonic neuronal lineages in the Drosophila thoracic central nervous system. Development 141, 1011–1021 (2014).
Lee, Y. J. et al. Conservation and divergence of related neuronal lineages in the Drosophila central brain. eLife 9, e53518 (2020).
Truman, J. W., Moats, W., Altman, J., Marin, E. C. & Williams, D. W. Role of Notch signaling in establishing the hemilineages of secondary neurons in Drosophila melanogaster. Development 137, 53–61 (2010).
Bentivoglio, M. & Mazzarello, P. The history of radial glia. Brain Res. Bull. 49, 305–315 (1999).
Alexandre, P., Reugels, A. M., Barker, D., Blanc, E. & Clarke, J. D. Neurons derive from the more apical daughter in asymmetric divisions in the zebrafish neural tube. Nat. Neurosci. 13, 673–679 (2010).
Dong, Z., Yang, N., Yeo, S. Y., Chitnis, A. & Guo, S. Intralineage directional Notch signaling regulates self-renewal and differentiation of asymmetrically dividing radial glia. Neuron 74, 65–78 (2012).
Kimura, Y., Satou, C. & Higashijima, S. V2a and V2b neurons are generated by the final divisions of pair-producing progenitors in the zebrafish spinal cord. Development 135, 3001–3005 (2008).
Demski, L. S. & Beaver, J. A. The cytoarchitecture of the tectal-related pallium of squirrelfish, Holocentrus sp. Front. Neuroanat. 16, 819365 (2022).
Sukhum, K. V., Shen, J. & Carlson, B. A. Extreme enlargement of the cerebellum in a clade of teleost fishes that evolved a novel active sensory system. Curr. Biol. 28, 3857–3863.e3 (2018).
Naumann, R. K. et al. The reptilian brain. Curr. Biol. 25, R317–R321 (2015).
Benito-Gutierrez, E. et al. The dorsoanterior brain of adult amphioxus shares similarities in expression profile and neuronal composition with the vertebrate telencephalon. BMC Biol. 19, 110 (2021).
Briscoe, S. D. & Ragsdale, C. W. Evolution of the chordate telencephalon. Curr. Biol. 29, R647–R662 (2019).
Cardenas, A. et al. Evolution of cortical neurogenesis in amniotes controlled by Robo signaling levels. Cell 174, 590–606.e21 (2018).
Nomura, T., Gotoh, H. & Ono, K. Changes in the regulation of cortical neurogenesis contribute to encephalization during amniote brain evolution. Nat. Commun. 4, 2206 (2013).
Garcia-Moreno, F. & Molnar, Z. Variations of telencephalic development that paved the way for neocortical evolution. Prog. Neurobiol. 194, 101865 (2020).
Cheung, A. F. P., Pollen, A. A., Tavare, A., DeProto, J. & Molnár, Z. Comparative aspects of cortical neurogenesis in vertebrates. J. Anat. 211, 164–176 (2007).
Martinez-Cerdeno, V. & Noctor, S. C. Cortical evolution 2015: discussion of neural progenitor cell nomenclature. J. Comp. Neurol. 524, 704–709 (2016).
Nomura, T. et al. The evolution of basal progenitors in the developing non-mammalian brain. Development 143, 66–74 (2016).
Striedter, G. F. & Charvet, C. J. Telencephalon enlargement by the convergent evolution of expanded subventricular zones. Biol. Lett. 5, 134–137 (2009).
Das, R. M. & Storey, K. G. Apical abscission alters cell polarity and dismantles the primary cilium during neurogenesis. Science 343, 200–204 (2014).
Le Dreau, G., Saade, M., Gutierrez-Vallejo, I. & Marti, E. The strength of SMAD1/5 activity determines the mode of stem cell division in the developing spinal cord. J. Cell Biol. 204, 591–605 (2014).
Saade, M. et al. Sonic hedgehog signaling switches the mode of division in the developing nervous system. Cell Rep. 4, 492–503 (2013).
Gotz, M. & Huttner, W. B. The cell biology of neurogenesis. Nat. Rev. Mol. Cell Biol. 6, 777–788 (2005).
Llinares-Benadero, C. & Borrell, V. Deconstructing cortical folding: genetic, cellular and mechanical determinants. Nat. Rev. Neurosci. 20, 161–176 (2019).
Franco, S. J. & Muller, U. Shaping our minds: stem and progenitor cell diversity in the mammalian neocortex. Neuron 77, 19–34 (2013).
Taverna, E., Gotz, 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, 465–502 (2014).
Betizeau, M. et al. Precursor diversity and complexity of lineage relationships in the outer subventricular zone of the primate. Neuron 80, 442–457 (2013).
Baala, L. et al. Homozygous silencing of T-box transcription factor EOMES leads to microcephaly with polymicrogyria and corpus callosum agenesis. Nat. Genet. 39, 454–456 (2007).
Lui, J. H., Hansen, D. V. & Kriegstein, A. R. Development and evolution of the human neocortex. Cell 146, 18–36 (2011).
Cheung, A. F. et al. The subventricular zone is the developmental milestone of a 6-layered neocortex: comparisons in metatherian and eutherian mammals. Cereb. Cortex 20, 1071–1081 (2010).
Dos Santos, S. E. et al. Cellular scaling rules for the brains of marsupials: not as “primitive” as expected. Brain Behav. Evol. 89, 48–63 (2017).
Paolino, A. et al. Non-uniform temporal scaling of developmental processes in the mammalian cortex. Nat. Commun. 14, 5950 (2023).
Puzzolo, E. & Mallamaci, A. Cortico-cerebral histogenesis in the opossum Monodelphis domestica: generation of a hexalaminar neocortex in the absence of a basal proliferative compartment. Neural Dev. 5, 8 (2010).
Sauerland, C. et al. The basal radial glia occurs in marsupials and underlies the evolution of an expanded neocortex in therian mammals. Cereb. Cortex 28, 145–157 (2018).
Saunders, N. R., Adam, E., Reader, M. & Mollgard, K. Monodelphis domestica (grey short-tailed opossum): an accessible model for studies of early neocortical development. Anat. Embryol. 180, 227–236 (1989).
deAzevedo, L. C. et al. Cortical radial glial cells in human fetuses: depth-correlated transformation into astrocytes. J. Neurobiol. 55, 288–298 (2003).
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, 1219–1227 (2016).
Bilgic, M. et al. Truncated radial glia as a common precursor in the late corticogenesis of gyrencephalic mammals. eLife 12, e91406 (2023).
Nowakowski, T. J. et al. Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex. Science 358, 1318–1323 (2017).
Pebworth, M. P., Ross, J., Andrews, M., Bhaduri, A. & Kriegstein, A. R. Human intermediate progenitor diversity during cortical development. Proc. Natl Acad. Sci. USA 118, e2019415118 (2021).
Pollen, A. A. et al. Molecular identity of human outer radial glia during cortical development. Cell 163, 55–67 (2015).
Thomsen, E. R. et al. Fixed single-cell transcriptomic characterization of human radial glial diversity. Nat. Methods 13, 87–93 (2016).
Fietz, S. A. & Huttner, W. B. Cortical progenitor expansion, self-renewal and neurogenesis—a polarized perspective. Curr. Opin. Neurobiol. 21, 23–35 (2011).
LaMonica, B. E., Lui, J. H., Wang, X. & Kriegstein, A. R. OSVZ progenitors in the human cortex: an updated perspective on neurodevelopmental disease. Curr. Opin. Neurobiol. 22, 747–753 (2012).
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, 3683–3695 (2011).
Wang, X., Tsai, J. W., LaMonica, B. & Kriegstein, A. R. A new subtype of progenitor cell in the mouse embryonic neocortex. Nat. Neurosci. 14, 555–561 (2011).
vasistha, N. A. et al. Cortical and clonal contribution of Tbr2 expressing progenitors in the developing mouse brain. Cereb. Cortex 25, 3290–3302 (2015).
Martinez-Cerdeno, V. et al. Comparative analysis of the subventricular zone in rat, ferret and macaque: evidence for an outer subventricular zone in rodents. PLoS ONE 7, e30178 (2012).
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, 554–561 (2010).
Fietz, S. A. et al. OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling. Nat. Neurosci. 13, 690–699 (2010).
Smart, I. H. Proliferative characteristics of the ependymal layer during the early development of the spinal cord in the mouse. J. Anat. 111, 365–380 (1972).
Smart, I. H. Proliferative characteristics of the ependymal layer during the early development of the mouse neocortex: a pilot study based on recording the number, location and plane of cleavage of mitotic figures. J. Anat. 116, 67–91 (1973).
Smart, I. H. A pilot study of cell production by the ganglionic eminences of the developing mouse brain. J. Anat. 121, 71–84 (1976).
Tarabykin, V., Stoykova, A., Usman, N. & Gruss, P. Cortical upper layer neurons derive from the subventricular zone as indicated by Svet1 gene expression. Development 128, 1983–1993 (2001).
Wang, L., Bluske, K. K., Dickel, L. K. & Nakagawa, Y. Basal progenitor cells in the embryonic mouse thalamus—their molecular characterization and the role of neurogenins and Pax6. Neural Dev. 6, 35 (2011).
Zhou, X. et al. Cellular and molecular properties of neural progenitors in the developing mammalian hypothalamus. Nat. Commun. 11, 4063 (2020).
Xu, H. T. et al. Distinct lineage-dependent structural and functional organization of the hippocampus. Cell 157, 1552–1564 (2014).
Gao, P. et al. Deterministic progenitor behavior and unitary production of neurons in the neocortex. Cell 159, 775–788 (2014).
Lin, Y. et al. Behavior and lineage progression of neural progenitors in the mammalian cortex. Curr. Opin. Neurobiol. 66, 144–157 (2021).
Llorca, A. et al. A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture. eLife 8, e51381 (2019).
Mihalas, A. B. & Hevner, R. F. Clonal analysis reveals laminar fate multipotency and daughter cell apoptosis of mouse cortical intermediate progenitors. Development 145, dev164335 (2018).
Andrews, M. G., Subramanian, L., Salma, J. & Kriegstein, A. R. How mechanisms of stem cell polarity shape the human cerebral cortex. Nat. Rev. Neurosci. 23, 711–724 (2022).
Penisson, M., Ladewig, J., Belvindrah, R. & Francis, F. Genes and mechanisms involved in the generation and amplification of basal radial glial cells. Front. Cell Neurosci. 13, 381 (2019).
Vaid, S. & Huttner, W. B. Progenitor-based cell biological aspects of neocortex development and evolution. Front. Cell Dev. Biol. 10, 892922 (2022).
Molnar, Z. et al. New insights into the development of the human cerebral cortex. J. Anat. 235, 432–451 (2019).
Delaunay, D., Kawaguchi, A., Dehay, C. & Matsuzaki, F. Division modes and physical asymmetry in cerebral cortex progenitors. Curr. Opin. Neurobiol. 42, 75–83 (2017).
Mizutani, K., Yoon, K., Dang, L., Tokunaga, A. & Gaiano, N. Differential Notch signalling distinguishes neural stem cells from intermediate progenitors. Nature 449, 351–355 (2007).
Shimojo, H., Ohtsuka, T. & Kageyama, R. Oscillations in notch signaling regulate maintenance of neural progenitors. Neuron 58, 52–64 (2008).
Cheng, S. et al. Conditional inactivation of Pen-2 in the developing neocortex leads to rapid switch of apical progenitors to basal progenitors. J. Neurosci. 39, 2195–2207 (2019).
Tiberi, L. et al. BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets. Nat. Neurosci. 15, 1627–1635 (2012).
Bylund, M., Andersson, E., Novitch, B. G. & Muhr, J. Vertebrate neurogenesis is counteracted by Sox1–3 activity. Nat. Neurosci. 6, 1162–1168 (2003).
Ochiai, W. et al. Periventricular notch activation and asymmetric Ngn2 and Tbr2 expression in pair-generated neocortical daughter cells. Mol. Cell Neurosci. 40, 225–233 (2009).
Lacomme, M., Liaubet, L., Pituello, F. & Bel-Vialar, S. NEUROG2 drives cell cycle exit of neuronal precursors by specifically repressing a subset of cyclins acting at the G1 and S phases of the cell cycle. Mol. Cell Biol. 32, 2596–2607 (2012).
Nguyen, L. et al. p27kip1 independently promotes neuronal differentiation and migration in the cerebral cortex. Genes. Dev. 20, 1511–1524 (2006).
Siegenthaler, J. A., Tremper-Wells, B. A. & Miller, M. W. Foxg1 haploinsufficiency reduces the population of cortical intermediate progenitor cells: effect of increased p21 expression. Cereb. Cortex 18, 1865–1875 (2008).
Englund, C. et al. Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J. Neurosci. 25, 247–251 (2005).
Arnold, S. J. et al. The T-box transcription factor Eomes/Tbr2 regulates neurogenesis in the cortical subventricular zone. Genes. Dev. 22, 2479–2484 (2008).
Mihalas, A. B. et al. Intermediate progenitor cohorts differentially generate cortical layers and require Tbr2 for timely acquisition of neuronal subtype identity. Cell Rep. 16, 92–105 (2016).
Hevner, R. F. Intermediate progenitors and Tbr2 in cortical development. J. Anat. 235, 616–625 (2019).
Maric, D., Fiorio Pla, A., Chang, Y. H. & Barker, J. L. Self-renewing and differentiating properties of cortical neural stem cells are selectively regulated by basic fibroblast growth factor (FGF) signaling via specific FGF receptors. J. Neurosci. 27, 1836–1852 (2007).
Kang, W., Wong, L. C., Shi, S. H. & Hebert, J. M. The transition from radial glial to intermediate progenitor cell is inhibited by FGF signaling during corticogenesis. J. Neurosci. 29, 14571–14580 (2009).
Rash, B. G., Lim, H. D., Breunig, J. J. & Vaccarino, F. M. FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis. J. Neurosci. 31, 15604–15617 (2011).
Rash, B. G., Tomasi, S., Lim, H. D., Suh, C. Y. & Vaccarino, F. M. Cortical gyrification induced by fibroblast growth factor 2 in the mouse brain. J. Neurosci. 33, 10802–10814 (2013).
Lange, C., Huttner, W. B. & Calegari, F. Cdk4/cyclinD1 overexpression in neural stem cells shortens G1, delays neurogenesis, and promotes the generation and expansion of basal progenitors. Cell Stem Cell 5, 320–331 (2009).
Pilaz, L. J. et al. Forced G1-phase reduction alters mode of division, neuron number, and laminar phenotype in the cerebral cortex. Proc. Natl Acad. Sci. USA 106, 21924–21929 (2009).
Nonaka-Kinoshita, M. et al. Regulation of cerebral cortex size and folding by expansion of basal progenitors. EMBO J. 32, 1817–1828 (2013).
Lukaszewicz, A., Savatier, P., Cortay, V., Kennedy, H. & Dehay, C. Contrasting effects of basic fibroblast growth factor and neurotrophin 3 on cell cycle kinetics of mouse cortical stem cells. J. Neurosci. 22, 6610–6622 (2002).
Heng, X., Guo, Q., Leung, A. W. & Li, J. Y. Analogous mechanism regulating formation of neocortical basal radial glia and cerebellar Bergmann glia. eLife 6, e23253 (2017).
Matsumoto, N., Shinmyo, Y., Ichikawa, Y. & Kawasaki, H. Gyrification of the cerebral cortex requires FGF signaling in the mammalian brain. eLife 6, e29285 (2017).
Kelava, I. 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).
Konno, D. et al. Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nat. Cell Biol. 10, 93–101 (2008).
Kosodo, Y. & Huttner, W. B. Basal process and cell divisions of neural progenitors in the developing brain. Dev. Growth Differ. 51, 251–261 (2009).
Loulier, K. et al. β1 integrin maintains integrity of the embryonic neocortical stem cell niche. PLoS Biol. 7, e1000176 (2009).
Radakovits, R., Barros, C. S., Belvindrah, R., Patton, B. & Muller, U. Regulation of radial glial survival by signals from the meninges. J. Neurosci. 29, 7694–7705 (2009).
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. Cereb. Cortex 21, 1674–1694 (2011).
Kalebic, N. 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).
Stenzel, D., Wilsch-Brauninger, M., Wong, F. K., Heuer, H. & Huttner, W. B. Integrin αvβ3 and thyroid hormones promote expansion of progenitors in embryonic neocortex. Development 141, 795–806 (2014).
Moreno-Layseca, P. & Streuli, C. H. Signalling pathways linking integrins with cell cycle progression. Matrix Biol. 34, 144–153 (2014).
Tomasello, U. et al. miR-137 and miR-122, two outer subventricular zone non-coding RNAs, regulate basal progenitor expansion and neuronal differentiation. Cell Rep. 38, 110381 (2022).
Wagenfuhr, L., Meyer, A. K., Braunschweig, L., Marrone, L. & Storch, A. Brain oxygen tension controls the expansion of outer subventricular zone-like basal progenitors in the developing mouse brain. Development 142, 2904–2915 (2015).
Wang, L., Hou, S. & Han, Y. G. Hedgehog signaling promotes basal progenitor expansion and the growth and folding of the neocortex. Nat. Neurosci. 19, 888–896 (2016).
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, e54873 (2020).
Shimada, I. S. et al. Derepression of sonic hedgehog signaling upon Gpr161 deletion unravels forebrain and ventricular abnormalities. Dev. Biol. 450, 47–62 (2019).
Hirabayashi, Y. & Gotoh, Y. Epigenetic control of neural precursor cell fate during development. Nat. Rev. Neurosci. 11, 377–388 (2010).
Pereira, J. D. et al. Ezh2, the histone methyltransferase of PRC2, regulates the balance between self-renewal and differentiation in the cerebral cortex. Proc. Natl Acad. Sci. USA 107, 15957–15962 (2010).
Bruggeman, S. W. et al. Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice. Genes. Dev. 19, 1438–1443 (2005).
Fasano, C. A. et al. Bmi-1 cooperates with Foxg1 to maintain neural stem cell self-renewal in the forebrain. Genes. Dev. 23, 561–574 (2009).
Molofsky, A. V. et al. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425, 962–967 (2003).
Economides, K. D., Zeltser, L. & Capecchi, M. R. Hoxb13 mutations cause overgrowth of caudal spinal cord and tail vertebrae. Dev. Biol. 256, 317–330 (2003).
Isono, K. et al. Mammalian polyhomeotic homologues Phc2 and Phc1 act in synergy to mediate polycomb repression of Hox genes. Mol. Cell Biol. 25, 6694–6706 (2005).
Li, X. et al. Mammalian polycomb-like Pcl2/Mtf2 is a novel regulatory component of PRC2 that can differentially modulate polycomb activity both at the Hox gene cluster and at Cdkn2a genes. Mol. Cell Biol. 31, 351–364 (2011).
Suzuki, M. et al. Involvement of the Polycomb-group gene Ring1B in the specification of the anterior–posterior axis in mice. Development 129, 4171–4183 (2002).
Wang, J., Mager, J., Schnedier, E. & Magnuson, T. The mouse PcG gene Eed is required for Hox gene repression and extraembryonic development. Mamm. Genome 13, 493–503 (2002).
Mora, A. et al. Variational autoencoding of gene landscapes during mouse CNS development uncovers layered roles of Polycomb repressor complex 2. Nucleic Acids Res. 50, 1280–1296 (2022).
Eckler, M. J. & Chen, B. Fez family transcription factors: controlling neurogenesis and cell fate in the developing mammalian nervous system. Bioessays 36, 788–797 (2014).
Islam, M. M. & Zhang, C. L. TLX: a master regulator for neural stem cell maintenance and neurogenesis. Biochim. Biophys. Acta 1849, 210–216 (2015).
Kitamura, K. et al. Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. Nat. Genet. 32, 359–369 (2002).
Wang, W. & Lufkin, T. The murine Otp homeobox gene plays an essential role in the specification of neuronal cell lineages in the developing hypothalamus. Dev. Biol. 227, 432–449 (2000).
Bishop, K. M., Garel, S., Nakagawa, Y., Rubenstein, J. L. & O’Leary, D. D. Emx1 and Emx2 cooperate to regulate cortical size, lamination, neuronal differentiation, development of cortical efferents, and thalamocortical pathfinding. J. Comp. Neurol. 457, 345–360 (2003).
Manuel, M. N. et al. The transcription factor Foxg1 regulates telencephalic progenitor proliferation cell autonomously, in part by controlling Pax6 expression levels. Neural Dev. 6, 9 (2011).
Stenman, J. M., Wang, B. & Campbell, K. Tlx controls proliferation and patterning of lateral telencephalic progenitor domains. J. Neurosci. 23, 10568–10576 (2003).
Telley, L. et al. Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex. Science 364, eaav2522 (2019).
Kerimoglu, C. et al. H3 acetylation selectively promotes basal progenitor proliferation and neocortex expansion. Sci. Adv. 7, eabc6792 (2021).
Tapias, A. et al. Trrap-dependent histone acetylation specifically regulates cell-cycle gene transcription to control neural progenitor fate decisions. Cell Stem Cell 14, 632–643 (2014).
Fish, J. L., Dehay, C., Kennedy, H. & Huttner, W. B. Making bigger brains—the evolution of neural-progenitor-cell division. J. Cell Sci. 121, 2783–2793 (2008).
Florio, M., Borrell, V. & Huttner, W. B. Human-specific genomic signatures of neocortical expansion. Curr. Opin. Neurobiol. 42, 33–44 (2017).
Fietz, S. 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, 11836–11841 (2012).
Florio, M. et al. Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex. eLife 7, e32332 (2018).
Johnson, M. B. et al. Single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex. Nat. Neurosci. 18, 637–646 (2015).
Miller, J. A. et al. Transcriptional landscape of the prenatal human brain. Nature 508, 199–206 (2014).
Ochi, S., Manabe, S., Kikkawa, T. & Osumi, N. Thirty years’ history since the discovery of Pax6: from central nervous system development to neurodevelopmental disorders. Int. J. Mol. Sci. 23, 6115 (2022).
Wong, F. K. et al. Sustained Pax6 expression generates primate-like basal radial glia in developing mouse neocortex. PLoS Biol. 13, e1002217 (2015).
Krontira, A. C. et al. Human cortical neurogenesis is altered via glucocorticoid-mediated regulation of ZBTB16 expression. Neuron 112, 1426–1446.e11 (2024).
Stahl, R. et al. Trnp1 regulates expansion and folding of the mammalian cerebral cortex by control of radial glial fate. Cell 153, 535–549 (2013).
Esgleas, M. et al. Trnp1 organizes diverse nuclear membrane-less compartments in neural stem cells. EMBO J. 39, e103373 (2020).
Martinez-Martinez, M. A. et al. A restricted period for formation of outer subventricular zone defined by Cdh1 and Trnp1 levels. Nat. Commun. 7, 11812 (2016).
Currey, L., Thor, S. & Piper, M. TEAD family transcription factors in development and disease. Development 148, dev196675 (2021).
Kostic, M. et al. YAP activity is necessary and sufficient for basal progenitor abundance and proliferation in the developing neocortex. Cell Rep. 27, 1103–1118.e6 (2019).
Cubillos, P. et al. The growth factor epiregulin promotes basal progenitor cell proliferation in the developing neocortex. EMBO J. 43, 1388–1419 (2024).
Tsui, D., Vessey, J. P., Tomita, H., Kaplan, D. R. & Miller, F. D. FoxP2 regulates neurogenesis during embryonic cortical development. J. Neurosci. 33, 244–258 (2013).
Enard, W. et al. Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418, 869–872 (2002).
Konopka, G. et al. Human-specific transcriptional regulation of CNS development genes by FOXP2. Nature 462, 213–217 (2009).
Hodzic, D. et al. TBC1D3, a hominoid oncoprotein, is encoded by a cluster of paralogues located on chromosome 17q12. Genomics 88, 731–736 (2006).
Zody, M. C. et al. DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature 440, 1045–1049 (2006).
Ju, X. C. et al. The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice. eLife 5, e18197 (2016).
Liu, J. et al. The primate-specific gene TMEM14B marks outer radial glia cells and promotes cortical expansion and folding. Cell Stem Cell 21, 635–649.e8 (2017).
Florio, M. et al. Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion. Science 347, 1465–1470 (2015).
Fischer, J. et al. Human-specific ARHGAP11B ensures human-like basal progenitor levels in hominid cerebral organoids. EMBO Rep. 23, e54728 (2022).
Florio, M., Namba, T., Paabo, S., Hiller, M. & Huttner, W. B. A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification. Sci. Adv. 2, e1601941 (2016).
Heide, M. et al. Human-specific ARHGAP11B increases size and folding of primate neocortex in the fetal marmoset. Science 369, 546–550 (2020).
Kalebic, N. et al. Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex. eLife 7, e41241 (2018).
Xing, L. et al. Expression of human-specific ARHGAP11B in mice leads to neocortex expansion and increased memory flexibility. EMBO J. 40, e107093 (2021).
Namba, T. et al. Human-specific ARHGAP11B acts in mitochondria to expand neocortical progenitors by glutaminolysis. Neuron 105, 867–881.e9 (2020).
Namba, T., Nardelli, J., Gressens, P. & Huttner, W. B. Metabolic regulation of neocortical expansion in development and evolution. Neuron 109, 408–419 (2021).
Xing, L. et al. Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development. Nat. Commun. 15, 3468 (2024).
Van Heurck, R. et al. CROCCP2 acts as a human-specific modifier of cilia dynamics and mTOR signaling to promote expansion of cortical progenitors. Neuron 111, 65–80.e6 (2023).
Prufer, K. et al. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 505, 43–49 (2014).
Urbach, R. & Technau, G. M. Neuroblast formation and patterning during early brain development in Drosophila. Bioessays 26, 739–751 (2004).
Benito-Kwiecinski, S. et al. An early cell shape transition drives evolutionary expansion of the human forebrain. Cell 184, 2084–2102.e19 (2021).
Caviness, V. S. Jr, Takahashi, T. & Nowakowski, R. S. Numbers, time and neocortical neuronogenesis: a general developmental and evolutionary model. Trends Neurosci. 18, 379–383 (1995).
Rakic, P. A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution. Trends Neurosci. 18, 383–388 (1995).
Emery, N. J. Cognitive ornithology: the evolution of avian intelligence. Philos. Trans. R. Soc. Lond. B Biol. Sci. 361, 23–43 (2006).
Olkowicz, S. et al. Birds have primate-like numbers of neurons in the forebrain. Proc. Natl Acad. Sci. USA 113, 7255–7260 (2016).
Ke, F. F. S. et al. Embryogenesis and adult life in the absence of intrinsic apoptosis effectors BAX, BAK, and BOK. Cell 173, 1217–1230.e17 (2018).
Lewitus, E., Kelava, I., Kalinka, A. T., Tomancak, P. & Huttner, W. B. An adaptive threshold in mammalian neocortical evolution. PLoS Biol. 12, e1002000 (2014).
Fernandez, V. & Borrell, V. Developmental mechanisms of gyrification. Curr. Opin. Neurobiol. 80, 102711 (2023).
Han, S. et al. Proneural genes define ground-state rules to regulate neurogenic patterning and cortical folding. Neuron 109, 2847–2863.e11 (2021).
Friedrich, R. W., Jacobson, G. A. & Zhu, P. Circuit neuroscience in zebrafish. Curr. Biol. 20, R371–R381 (2010).
Kelava, I., Lewitus, E. & Huttner, W. B. The secondary loss of gyrencephaly as an example of evolutionary phenotypical reversal. Front. Neuroanat. 7, 16 (2013).
Vanderhaeghen, P. & Polleux, F. Developmental mechanisms underlying the evolution of human cortical circuits. Nat. Rev. Neurosci. 24, 213–232 (2023).
Haynes, E. M., Ulland, T. K. & Eliceiri, K. W. A model of discovery: the role of imaging established and emerging non-mammalian models in neuroscience. Front. Mol. Neurosci. 15, 867010 (2022).
Acknowledgements
S.T. thanks S. Temple, H. Wang, L. Fenlon and C. Q. Doe for advice or comments on the manuscript, and A. Kallstrand Thor for help with the illustrations.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
S.T. has received research grants from the Australian Research Council (DP220100985, DP230101750), the Australian National Health and Medical Research Council (230101750) and The University of Queensland, Australia.
Peer review
Peer review information
Nature Reviews Neuroscience thanks the anonymous reviewers for their contribution to the peer review of this work.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Thor, S. Indirect neurogenesis in space and time. Nat. Rev. Neurosci. (2024). https://doi.org/10.1038/s41583-024-00833-x
Accepted:
Published:
DOI: https://doi.org/10.1038/s41583-024-00833-x
