Neural tube morphogenesis in synthetic 3D microenvironments

Three-dimensional organoid constructs serve as increasingly widespread in vitro models for development and disease modeling. Current approaches to recreate morphogenetic processes in vitro rely on poorly controllable and ill-defined matrices, thereby largely overlooking the contribution of biochemic...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 113; no. 44; pp. E6831 - E6839
Main Authors Ranga, Adrian, Girgin, Mehmet, Meinhardt, Andrea, Eberle, Dominic, Caiazzo, Massimiliano, Tanaka, Elly M., Lutolf, Matthias P.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 01.11.2016
SeriesPNAS Plus
Subjects
Biochemistry
Biological Sciences
Chemical synthesis
Cytoskeleton
Matrix
Microenvironments
Morphogenesis
Physical Sciences
PNAS Plus
Symmetry
neural tube
development
embryonic stem cell
extracellular matrix
organoid
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Summary:Three-dimensional organoid constructs serve as increasingly widespread in vitro models for development and disease modeling. Current approaches to recreate morphogenetic processes in vitro rely on poorly controllable and ill-defined matrices, thereby largely overlooking the contribution of biochemical and biophysical extracellular matrix (ECM) factors in promoting multicellular growth and reorganization. Here, we show how defined synthetic matrices can be used to explore the role of the ECM in the development of complex 3D neuroepithelial cysts that recapitulate key steps in early neurogenesis. We demonstrate how key ECM parameters are involved in specifying cytoskeleton-mediated symmetry-breaking events that ultimately lead to neural tube-like patterning along the dorsal–ventral (DV) axis. Such synthetic materials serve as valuable tools for studying the discrete action of extrinsic factors in organogenesis, and allow for the discovery of relationships between cytoskeletal mechanobiology and morphogenesis.
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Author contributions: A.R., E.M.T., and M.P.L. designed research; A.R., M.G., D.E., and M.C. performed research; A.M. and D.E. contributed new reagents/analytic tools; A.R., E.M.T., and M.P.L. analyzed data; and A.R., E.M.T., and M.P.L. wrote the paper.
Edited by Brigid L. M. Hogan, Duke University Medical Center, Durham, NC, and approved August 5, 2016 (received for review March 2, 2016)
2Present address: Institute of Genetics and Biophysics, “A. Buzzati-Traverso,” Consiglio Nazionale delle Ricerche, 80131 Naples, Italy.
1Present address: Department of Mechanical Engineering, Biomechanics Section, KU Leuven, 3001 Leuven, Belgium.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1603529113