학술논문

Morphogenesis and development of human telencephalic organoids in the absence and presence of exogenous extracellular matrix.
Document Type
Article
Source
EMBO Journal. Nov2023, Vol. 42 Issue 22, p1-17. 17p.
Subject
*EXTRACELLULAR matrix
*ORGANOIDS
*NEURONAL differentiation
*BASAL lamina
*CEREBRAL cortex
*DEVELOPMENTAL neurobiology
*MORPHOGENESIS
Language
ISSN
0261-4189
Abstract
The establishment and maintenance of apical‐basal polarity is a fundamental step in brain development, instructing the organization of neural progenitor cells (NPCs) and the developing cerebral cortex. Particularly, basally located extracellular matrix (ECM) is crucial for this process. In vitro, epithelial polarization can be achieved via endogenous ECM production, or exogenous ECM supplementation. While neuroepithelial development is recapitulated in neural organoids, the effects of different ECM sources in tissue morphogenesis remain underexplored. Here, we show that exposure to a solubilized basement membrane matrix substrate, Matrigel, at early neuroepithelial stages causes rapid tissue polarization and rearrangement of neuroepithelial architecture. In cultures exposed to pure ECM components or unexposed to any exogenous ECM, polarity acquisition is slower and driven by endogenous ECM production. After the onset of neurogenesis, tissue architecture and neuronal differentiation are largely independent of the initial ECM source, but Matrigel exposure has long‐lasting effects on tissue patterning. These results advance the knowledge on mechanisms of exogenously and endogenously guided morphogenesis, demonstrating the self‐sustainability of neuroepithelial cultures by endogenous processes. Synopsis: Human telencephalic organoids can develop in the presence or absence of exogenous extracellular matrix (ECM) in the form of Matrigel. This work presents characterization of the short‐ and long‐term effects of exogenous ECM exposure on telencephalic organoid morphogenesis and differentiation. Matrigel triggers fast tissue morphogenesis at early developmental stages, which occur with a 5‐ to 7‐day delay in unexposed organoids.In the absence of Matrigel, endogenous processes of ECM production and rearrangement support tissue morphogenesis and growth.The effects of Matrigel are likely multifactorial and cannot be replaced by isolated Matrigel components.In long‐term cultures, organoids grown in the presence or absence of Matrigel establish the same repertoires of telencephalic cell types and do not display any striking morphological differences. [ABSTRACT FROM AUTHOR]