The shapes of elongating gastruloids are consistent with convergent extension driven by a combination of active cell crawling and differential adhesion

伸长的类原肠胚的形状与由主动细胞爬行和差异粘附共同驱动的收敛延伸相一致

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作者:Martijn A de Jong, Esmée Adegeest, Noémie M L P Bérenger-Currias, Maria Mircea, Roeland M H Merks, Stefan Semrau

Abstract

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.

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