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.
Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):E6831-E6839.
Ranga A, Girgin M, Meinhardt A, Eberle D, Caiazzo M, Tanaka EM, Lutolf MP
Curr Opin Genet Dev. 2019 Mar 4;54:7-11. doi: 10.1016/j.gde.2019.02.003
Commun Biol. 2019 Feb 25;2:78. doi: 10.1038/s42003-019-0305-x. eCollection 2019.
Ann Surg Oncol. 2019 Jan;26(1):139-147. doi: 10.1245/s10434-018-7008-2. Epub 2018 Nov 9.
Nature 561, S48-S49 (2018); doi: 10.1038/d41586-018-06708-3
Human Molecular Genetics, Volume 27, Issue R2, 01 August 2018, Pages R99–R107
Nature Reviews Cancervolume 18, pages407–418 (2018)
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