The authors tested their system by focusing on neural tube formation. Neural induction in the system replicates in vivo neurulation Therefore, the engineered system possesses all the attributes to make it a reliable in vitro model to study the dynamics of organ morphogenesis. Importantly, they found the central lumen to be physically and chemically isolated from the external environment, allowing the study of niche-mediated regulation of fate specification and tissue morphogenesis. Sustained maintenance of pluripotency implies the flexibility of the experimental model, allowing the differentiation towards any organ or tissue of interest. This 3D tissue stained positively for the core pluripotency factors: Oct4, Sox2, and Nanog. Matrigel was supplied to trigger 3D transition, which eventually generated a pluripotent epithelium surrounding a lumen.
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To recapitulate this in their model system, the authors cultured PSCs in 2D on micropatterned protein islands. The cell number, size, and shape of primary embryonic tissue, from which organs develop, are tightly regulated in vivo. Micropatterning PSC cultures yields a robust and versatile experimental system As a proof of concept, the authors supplemented the system with morphogens that drive early neural development and by monitoring the system through long-term live imaging, the authors report the intricacies of neural tube folding. Through micropatterning of human Pluripotent Stem Cells (hPSCs), precise control over initial size, shape and cell number was achieved, leading to high reproducibility of resultant tissue patterns. In this preprint, the authors present a new experimental system to faithfully study the dynamics of organ morphogenesis in vitro. Pluripotent Stem Cells (PSCs) are the ideal starting material for such a system, given they can generate all the founder lineages and any subsequent organ of interest. Developing an alternative experimental model which can overcome the limitations of these existing systems would therefore prove useful for understanding certain aspects of human development.
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Other experimental models such as organ-on-chip, which are scalable and can be controlled to generate functional tissues, impose additional constraints preventing the self-organization observed in embryonic development.
![francis ching geometric organization francis ching geometric organization](https://www.perlego.com/books/RM_Books/taylor_and_francis_daksqju/9781000691115.jpg)
Animal models are also limited by their relevance to human development. Although organoids offer an alternative for recapitulating organ formation, the resultant tissue shape and cell fate patterns are anatomically incorrect with low reproducibility. To try and overcome this, various alternative systems have been developed to try and aid our understanding of organ developmental processes. However, technical challenges hinder the accessibility of the respective cell types involved in human embryos, thereby impeding the study of this process in the native in vivo context. Errors in neural tubulation can lead to disability and/or postnatal lethality, and hence warrants a better understanding at cell- and tissue-level. Neural tube folding, the foundational event for the development of the brain and spinal cord, is one such example. Understanding the morphogenetic events underlying de novo organ formation during human embryonic development is a topic of immense interest.