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.

中文翻译：

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外源细胞外基质不存在和存在下人类端脑类器官的形态发生和发育

顶端-基底极性的建立和维持是大脑发育的基本步骤，指导神经祖细胞（NPC）的组织和发育中的大脑皮层。特别是，位于基底的细胞外基质（ECM）对于这一过程至关重要。在体外，上皮极化可以通过内源性 ECM 产生或外源性 ECM 补充来实现。虽然神经上皮发育在神经类器官中得到了重现，但不同 ECM 来源对组织形态发生的影响仍未得到充分探索。在这里，我们表明，在早期神经上皮阶段暴露于可溶的基底膜基质基质基质胶会导致快速组织极化和神经上皮结构的重新排列。在暴露于纯 ECM 成分或未暴露于任何外源 ECM 的培养物中，极性获取较慢，并由内源 ECM 产生驱动。神经发生开始后，组织结构和神经元分化在很大程度上独立于最初的 ECM 来源，但基质胶暴露对组织模式具有长期持续的影响。这些结果推进了关于外源性和内源性引导形态发生机制的知识，证明了神经上皮培养物通过内源性过程的自我维持。