Neural tube morphogenesis in synthetic 3D microenvironments

Abstract

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.

Three‐Dimensional Models of the Human Brain Development and Diseases

“…[197,200,201] Modular synthetic matrices have been used to control early neural morphogenesis and to explore the role of ECM in the development of 3D neuroepithelial organoids. [200,201] A recent study used a 3D microarray platform based on cross-linked multi-arm PEG, to probe the effect of factors including matrix elasticity, degradability, and signaling proteins on mouse embryonic stem cells (Figure 7D). [201] Current approaches to study the neural tube morphogenesis also rely on commercial animal derived matrices, such as Matrigel.…”

“…[200,201] A recent study used a 3D microarray platform based on cross-linked multi-arm PEG, to probe the effect of factors including matrix elasticity, degradability, and signaling proteins on mouse embryonic stem cells (Figure 7D). [201] Current approaches to study the neural tube morphogenesis also rely on commercial animal derived matrices, such as Matrigel. However, Matrigel leads to heterogeneities, whereas well defined synthetic matrices lead to more homogeneous and defined populations.…”

“…New insights are emerging into the role of biophysical factors in neural morphogenesis and multifactorial cell-matrix interactions are key to control the growth and differentiation of stem cells in vitro. [201] …”

357 Occupational exposure to selenium compounds, its effect on biological parameters and markers of diabetes

“…Embryonic and extraembryonic stem cells have been shown to self-organize in 3D culture (45)(46)(47)(48)(49). When ESCs are cultured in a 3D gel supplemented with ECM, they form an apicalbasal polarized shell that eliminates the boundaries of micropattern culture, allowing control of substrate mechanics and chemistry.…”

Dynamic bioengineered hydrogels as scaffolds for advanced stem cell and organoid culture

“…Recently, hydrogels have been used to investigate the role of the ECM on the formation of self-organized multi-cellular aggregates. [2] By tuning matrix stiffness, degradability, and type and amount of biologically active ligand, the optimal conditions for proliferation, differentiation, and self-organization can be identified. Interestingly, the optimal hydrogel compositions vary significantly for different cell types, reflecting the advantage of specifically bioengineered matrices over Matrigel.…”