Cao Dominica, Garai Sumit, DiFrisco James, Veenvliet Jesse V
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Theoretical Biology Lab, The Francis Crick Institute, London NW1 1AT, UK.
Interface Focus. 2024 Oct 25;14(5):20240023. doi: 10.1098/rsfs.2024.0023. eCollection 2024 Oct 11.
Organoids and stem-cell-based embryo models (SEMs) are imperfect organ or embryo representations that explore a much larger space of possible forms, or morphospace, compared to their counterparts. Here, we discuss SEM biology in light of seminal work by Pere Alberch, a leading figure in early evo-devo, interpreting SEMs as developmental 'monstrosities' in the Alberchian sense. Alberch suggested that ordered patterns in aberrant development-i.e. 'the logic of monsters'-reveal developmental constraints on possible morphologies. In the same vein, we detail how SEMs have begun to shed light on structural features of normal development, such as developmental variability, the relative importance of internal versus external constraints, boundary conditions and design principles governing robustness and canalization. We argue that SEMs represent a powerful experimental tool to explore and expand developmental morphospace and propose that the 'monstrosity' of SEMs can be leveraged to uncover the 'hidden' rules and developmental constraints that robustly shape and pattern the embryo.
类器官和基于干细胞的胚胎模型（SEMs）是不完美的器官或胚胎表征，与它们的对应物相比，它们探索了更大的可能形式空间，即形态空间。在这里，我们根据早期进化发育生物学的领军人物佩雷·阿尔贝奇的开创性工作来讨论SEMs生物学，将SEMs解释为阿尔贝奇意义上的发育“畸形”。阿尔贝奇认为，异常发育中的有序模式，即“怪物的逻辑”，揭示了对可能形态的发育限制。同样，我们详细阐述了SEMs如何开始阐明正常发育的结构特征，如发育变异性、内部与外部限制的相对重要性、边界条件以及支配稳健性和定向化的设计原则。我们认为，SEMs是探索和扩展发育形态空间的强大实验工具，并提出可以利用SEMs的“畸形”来揭示稳健塑造胚胎形态和模式的“隐藏”规则和发育限制。
