2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2016 Apr 7

PMID 27049876

Citations 155

Authors

Tomoki Otani

Maria C Marchetto

Fred H Gage

Benjamin D Simons

Frederick J Livesey

Affiliations

Soon will be listed here.

Abstract

Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.

Citing Articles

Emerging brain organoids: 3D models to decipher, identify and revolutionize brain.

Zhao Y, Wang T, Liu J, Wang Z, Lu Y Bioact Mater. 2025; 47:378-402.

PMID: 40026825 PMC: 11869974. DOI: 10.1016/j.bioactmat.2025.01.025.

Modelling human brain development and disease with organoids.

Birtele M, Lancaster M, Quadrato G Nat Rev Mol Cell Biol. 2024; .

PMID: 39668188 DOI: 10.1038/s41580-024-00804-1.

INTERSPECIES ORGANOIDS REVEAL HUMAN-SPECIFIC MOLECULAR FEATURES OF DOPAMINERGIC NEURON DEVELOPMENT AND VULNERABILITY.

Nolbrant S, Wallace J, Ding J, Zhu T, Sevetson J, Kajtez J bioRxiv. 2024; .

PMID: 39605599 PMC: 11601475. DOI: 10.1101/2024.11.14.623592.

Transplanted deep-layer cortical neuroblasts integrate into host neural circuits and alleviate motor defects in hypoxic-ischemic encephalopathy injured mice.

Wu M, Xu Y, Ji X, Zhou Y, Li Y, Feng B Stem Cell Res Ther. 2024; 15(1):422.

PMID: 39533375 PMC: 11558921. DOI: 10.1186/s13287-024-04049-9.

What's so special about the human brain? A graphical guide.

Smith K, Spencer N Nature. 2024; .

PMID: 39478071 DOI: 10.1038/d41586-024-03425-y.

References

Workman A, Charvet C, Clancy B, Darlington R, Finlay B . Modeling transformations of neurodevelopmental sequences across mammalian species. J Neurosci. 2013; 33(17):7368-83. PMC: 3928428. DOI: 10.1523/JNEUROSCI.5746-12.2013. View

Dehay C, Kennedy H, Kosik K . The outer subventricular zone and primate-specific cortical complexification. Neuron. 2015; 85(4):683-94. DOI: 10.1016/j.neuron.2014.12.060. View

Keeney J, Davis J, Siegenthaler J, Post M, Nielsen B, Hopkins W . DUF1220 protein domains drive proliferation in human neural stem cells and are associated with increased cortical volume in anthropoid primates. Brain Struct Funct. 2014; 220(5):3053-60. PMC: 4722867. DOI: 10.1007/s00429-014-0814-9. View

Barreto-Chang O, Dolmetsch R . Calcium imaging of cortical neurons using Fura-2 AM. J Vis Exp. 2009; (23). PMC: 2763293. DOI: 10.3791/1067. View

Florio M, Huttner W . Neural progenitors, neurogenesis and the evolution of the neocortex. Development. 2014; 141(11):2182-94. DOI: 10.1242/dev.090571. View

Boyd J, Skove S, Rouanet J, Pilaz L, Bepler T, Gordan R . Human-chimpanzee differences in a FZD8 enhancer alter cell-cycle dynamics in the developing neocortex. Curr Biol. 2015; 25(6):772-779. PMC: 4366288. DOI: 10.1016/j.cub.2015.01.041. View

Herculano-Houzel S . The human brain in numbers: a linearly scaled-up primate brain. Front Hum Neurosci. 2009; 3:31. PMC: 2776484. DOI: 10.3389/neuro.09.031.2009. View

Molyneaux B, Arlotta P, Menezes J, Macklis J . Neuronal subtype specification in the cerebral cortex. Nat Rev Neurosci. 2007; 8(6):427-37. DOI: 10.1038/nrn2151. View

Azevedo F, Carvalho L, Grinberg L, Farfel J, Ferretti R, Leite R . Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J Comp Neurol. 2009; 513(5):532-41. DOI: 10.1002/cne.21974. View

10.

Smart I, 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. Cereb Cortex. 2001; 12(1):37-53. PMC: 1931430. DOI: 10.1093/cercor/12.1.37. View

11.

McConnell S . The control of neuronal identity in the developing cerebral cortex. Curr Opin Neurobiol. 1992; 2(1):23-7. DOI: 10.1016/0959-4388(92)90156-f. View

12.

Rakic P . Radial unit hypothesis of neocortical expansion. Novartis Found Symp. 2000; 228:30-42; discussion 42-52. DOI: 10.1002/0470846631.ch3. View

13.

Noctor S, Martinez-Cerdeno V, Ivic L, Kriegstein A . Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci. 2004; 7(2):136-44. DOI: 10.1038/nn1172. View

14.

Espuny-Camacho I, Michelsen K, Gall D, Linaro D, Hasche A, Bonnefont J . Pyramidal neurons derived from human pluripotent stem cells integrate efficiently into mouse brain circuits in vivo. Neuron. 2013; 77(3):440-56. DOI: 10.1016/j.neuron.2012.12.011. View

15.

Mariani J, Simonini M, Palejev D, Tomasini L, Coppola G, Szekely A . Modeling human cortical development in vitro using induced pluripotent stem cells. Proc Natl Acad Sci U S A. 2012; 109(31):12770-5. PMC: 3411972. DOI: 10.1073/pnas.1202944109. View

16.

Kornack D, Rakic P . Radial and horizontal deployment of clonally related cells in the primate neocortex: relationship to distinct mitotic lineages. Neuron. 1995; 15(2):311-21. DOI: 10.1016/0896-6273(95)90036-5. View

17.

Nowakowski R, Lewin S, Miller M . Bromodeoxyuridine immunohistochemical determination of the lengths of the cell cycle and the DNA-synthetic phase for an anatomically defined population. J Neurocytol. 1989; 18(3):311-8. DOI: 10.1007/BF01190834. View

18.

Kirwan P, Turner-Bridger B, Peter M, Momoh A, Arambepola D, Robinson H . Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro. Development. 2015; 142(18):3178-87. PMC: 4582178. DOI: 10.1242/dev.123851. View

19.

McConnell S . Development and decision-making in the mammalian cerebral cortex. Brain Res. 1988; 472(1):1-23. DOI: 10.1016/0165-0173(88)90002-1. View

20.

Qian X, Goderie S, Shen Q, Stern J, Temple S . Intrinsic programs of patterned cell lineages in isolated vertebrate CNS ventricular zone cells. Development. 1998; 125(16):3143-52. DOI: 10.1242/dev.125.16.3143. View