Human neural tube morphogenesis in vitro by geometric constraints

Eyal Karzbrun (), Aimal H. Khankhel, Heitor C. Megale, Stella M. K. Glasauer, Yofiel Wyle, George Britton, Aryeh Warmflash, Kenneth S. Kosik, Eric D. Siggia, Boris I. Shraiman and Sebastian J. Streichan ()
Additional contact information
Eyal Karzbrun: University of California Santa Barbara
Aimal H. Khankhel: University of California Santa Barbara
Heitor C. Megale: University of California Santa Barbara
Stella M. K. Glasauer: University of California Santa Barbara
Yofiel Wyle: University of California Santa Barbara
George Britton: Rice University Houston
Aryeh Warmflash: Rice University Houston
Kenneth S. Kosik: University of California Santa Barbara
Eric D. Siggia: The Rockefeller University
Boris I. Shraiman: University of California Santa Barbara
Sebastian J. Streichan: University of California Santa Barbara

Nature, 2021, vol. 599, issue 7884, 268-272

Abstract: Abstract Understanding human organ formation is a scientific challenge with far-reaching medical implications1,2. Three-dimensional stem-cell cultures have provided insights into human cell differentiation3,4. However, current approaches use scaffold-free stem-cell aggregates, which develop non-reproducible tissue shapes and variable cell-fate patterns. This limits their capacity to recapitulate organ formation. Here we present a chip-based culture system that enables self-organization of micropatterned stem cells into precise three-dimensional cell-fate patterns and organ shapes. We use this system to recreate neural tube folding from human stem cells in a dish. Upon neural induction5,6, neural ectoderm folds into a millimetre-long neural tube covered with non-neural ectoderm. Folding occurs at 90% fidelity, and anatomically resembles the developing human neural tube. We find that neural and non-neural ectoderm are necessary and sufficient for folding morphogenesis. We identify two mechanisms drive folding: (1) apical contraction of neural ectoderm, and (2) basal adhesion mediated via extracellular matrix synthesis by non-neural ectoderm. Targeting these two mechanisms using drugs leads to morphological defects similar to neural tube defects. Finally, we show that neural tissue width determines neural tube shape, suggesting that morphology along the anterior–posterior axis depends on neural ectoderm geometry in addition to molecular gradients7. Our approach provides a new route to the study of human organ morphogenesis in health and disease.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41586-021-04026-9 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:599:y:2021:i:7884:d:10.1038_s41586-021-04026-9

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-04026-9

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().