Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jan;63(1):18-25.
doi: 10.1111/dgd.12699. Epub 2020 Nov 22.

Modeling neurodevelopment in a dish with pluripotent stem cells

Kent Imaizumi  1 , Hideyuki Okano  1
Affiliations
Review

Modeling neurodevelopment in a dish with pluripotent stem cells

Kent Imaizumi et al. Dev Growth Differ. 2021 Jan.

Abstract

Pluripotent stem cells (PSCs) can differentiate into all cell types in the body, and their differentiation procedures recapitulate the developmental processes of embryogenesis. Focusing on neurodevelopment, we describe here the application of knowledge gained from embryology to the neural induction of PSCs. Furthermore, PSC-based neural modeling provides novel insights into neurodevelopmental processes. In particular, human PSC cultures are a powerful tool for the study of human-specific neurodevelopmental processes and could even enable the elucidation of the mechanisms of human brain evolution. We also discuss challenges and potential future directions in further improving PSC-based neural modeling.

Keywords: human-specific neurodevelopment; neural specification; pluripotent stem cell; regional patterning.

PubMed Disclaimer

Conflict of interest statement

H.O. is a compensated scientific consultant for San Bio Co. Ltd. and K Pharma Inc. K.I. declared no potential conflicts of interest.

Figures

Figure 1
Figure 1
Directed differentiation of PSCs into the neural lineage by dual SMAD inhibition. Schematic for neural differentiation from PSCs. Dual SMAD inhibition leads to the selective induction of neuroectoderm by the prevention of non‐neural lineages. SB431542 and Noggin were initially used in the original report by Studer and colleagues, and other small‐molecule inhibitors targeting specific SMAD signaling pathways have now also been used
Figure 2
Figure 2
Regional control of PSC‐derived neural cells. (a) Signaling gradients along the anteroposterior (A‐P) and dorsoventral (D‐V) axes pattern the regional identity in the nervous system. (b) The control of A‐P and D‐V patterning signaling during neural induction enables the generation of any desired brain regions from PSCs
Figure 3
Figure 3
Characteristic neurodevelopmental processes in humans. Human PSC‐based neural models exhibit a prolonged period of progenitor expansion, the derivation of deep layer projection neurons from the subplate, and long‐term morphological/functional maturation, which may reflect the existence of outer radial glia (oRG) cells, the distinct regulation of deep layer neuron specification, and the human brain neoteny or retention of developmental traits into adulthood, respectively
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Asashima, M. , Nakano, H. , Shimada, K. , Kinoshita, K. , Ishii, K. , Shibai, H. , & Ueno, N. (1990). Mesodermal induction in early amphibian embryos by activin A (erythroid differentiation factor). Roux’s Archives of Developmental Biology, 198(6), 330–335. 10.1007/BF00383771 - DOI - PubMed
    1. Avantaggiato, V. , Acampora, D. , Tuorto, F. , & Simeone, A. (1996). Retinoic acid induces stage‐specific repatterning of the rostral central nervous system. Developmental Biology, 175(2), 347–357. 10.1006/dbio.1996.0120 - DOI - PubMed
    1. Bagley, J. A. , Reumann, D. , Bian, S. , Lévi‐Strauss, J. , & Knoblich, J. A. (2017). Fused cerebral organoids model interactions between brain regions. Nature Methods, 14(7), 743–751. 10.1038/nmeth.4304 - DOI - PMC - PubMed
    1. Bain, G. , Kitchens, D. , Yao, M. , Huettner, J. E. , & Gottlieb, D. I. (1995). Embryonic stem cells express neuronal properties in vitro. Developmental Biology, 168(2), 342–357. 10.1006/dbio.1995.1085 - DOI - PubMed
    1. Birey, F. , Andersen, J. , Makinson, C. D. , Islam, S. , Wei, W. U. , Huber, N. , Fan, H. C. , Metzler, K. R. C. , Panagiotakos, G. , Thom, N. , O’Rourke, N. A. , Steinmetz, L. M. , Bernstein, J. A. , Hallmayer, J. , Huguenard, J. R. , & Paşca, S. P. (2017). Assembly of functionally integrated human forebrain spheroids. Nature, 545(7652), 54–59. 10.1038/nature22330 - DOI - PMC - PubMed