Human neural tube morphogenesis in vitro by geometric constraints.

Autor: Karzbrun E; Department of Physics, University of California Santa Barbara, Santa Barbara, CA, USA. karzbrun@gmail.com.; Kavli Institute for Theoretical Physics, Santa Barbara, CA, USA. karzbrun@gmail.com., Khankhel AH; Biomolecular Science and Engineering, University of California Santa Barbara, Santa Barbara, CA, USA., Megale HC; Department of Physics, University of California Santa Barbara, Santa Barbara, CA, USA., Glasauer SMK; Department of Molecular, Cellular, Developmental Biology, University of California Santa Barbara, Santa Barbara, CA, USA.; Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, USA., Wyle Y; Department of Molecular, Cellular, Developmental Biology, University of California Santa Barbara, Santa Barbara, CA, USA., Britton G; Systems Synthetic and Physical Biology Program, Rice University Houston, Houston, TX, USA., Warmflash A; Department of Biosciences, Rice University Houston, Houston, TX, USA.; Department of Bioengineering, Rice University Houston, Houston, TX, USA., Kosik KS; Department of Molecular, Cellular, Developmental Biology, University of California Santa Barbara, Santa Barbara, CA, USA.; Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, USA., Siggia ED; Center for Studies in Physics and Biology, The Rockefeller University, New York, NY, USA., Shraiman BI; Department of Physics, University of California Santa Barbara, Santa Barbara, CA, USA.; Kavli Institute for Theoretical Physics, Santa Barbara, CA, USA., Streichan SJ; Department of Physics, University of California Santa Barbara, Santa Barbara, CA, USA. streicha@ucsb.edu.; Biomolecular Science and Engineering, University of California Santa Barbara, Santa Barbara, CA, USA. streicha@ucsb.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2021 Nov; Vol. 599 (7884), pp. 268-272. Date of Electronic Publication: 2021 Oct 27.
DOI: 10.1038/s41586-021-04026-9
Abstrakt: Understanding human organ formation is a scientific challenge with far-reaching medical implications 1,2 . Three-dimensional stem-cell cultures have provided insights into human cell differentiation 3,4 . 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 induction 5,6 , 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 gradients 7 . Our approach provides a new route to the study of human organ morphogenesis in health and disease.
(© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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