Mathematical Institute, Leiden University, Leiden, The Netherlands.
Leiden Institute of Physics, Leiden University, Leiden, The Netherlands.
PLoS Comput Biol. 2024 Feb 2;20(2):e1011825. doi: 10.1371/journal.pcbi.1011825. eCollection 2024 Feb.
Gastruloids have emerged as highly useful in vitro models of mammalian gastrulation. One of the most striking features of 3D gastruloids is their elongation, which mimics the extension of the embryonic anterior-posterior axis. Although axis extension is crucial for development, the underlying mechanism has not been fully elucidated in mammalian species. Gastruloids provide an opportunity to study this morphogenic process in vitro. Here, we measure and quantify the shapes of elongating gastruloids and show, by Cellular Potts model simulations based on a novel, optimized algorithm, that convergent extension, driven by a combination of active cell crawling and differential adhesion can explain the observed shapes. We reveal that differential adhesion alone is insufficient and also directly observe hallmarks of convergent extension by time-lapse imaging of gastruloids. Finally, we show that gastruloid elongation can be abrogated by inhibition of the Rho kinase pathway, which is involved in convergent extension in vivo. All in all, our study demonstrates, how gastruloids can be used to elucidate morphogenic processes in embryonic development.
类囊胚已成为研究哺乳动物原肠胚形成的非常有用的体外模型。3D 类囊胚最显著的特征之一是其伸长，这模拟了胚胎前后轴的延伸。尽管轴延伸对发育至关重要，但哺乳动物物种中的这一潜在机制尚未完全阐明。类囊胚为体外研究这一形态发生过程提供了机会。在这里，我们测量和量化了伸长类囊胚的形状，并通过基于新的优化算法的细胞Potts 模型模拟表明，由活性细胞爬行和差异粘附驱动的趋同延伸可以解释所观察到的形状。我们揭示了单独的差异粘附是不够的，并且还通过对类囊胚的延时成像直接观察到趋同延伸的特征。最后，我们表明通过抑制 Rho 激酶途径可以阻断类囊胚的伸长，该途径参与体内的趋同延伸。总而言之，我们的研究表明，类囊胚如何用于阐明胚胎发育中的形态发生过程。
