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Adegeest, E.

Publications and source records attributed to Adegeest, E..

2 recordsLinked to original sources

A combination of convergent extension and differential adhesion explains the shapes of elongating gastruloids

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, that a combination of convergent extension 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.

developmental biology↗

Early neurulation recapitulated in assemblies of embryonic and extraembryonic cells

Stem-cell derived in vitro systems, such as organoids or embryoids, hold great potential for modeling in vivo biology and engineering living systems with novel functions. To unlock that potential, we need new ways to elicit higher-level organization. Here we show that adding extraembryonic endoderm (XEN) cells to mouse gastruloids leads to the formation of neural epithelia. By single-cell RNA-seq, imaging and differentiation experiments, we demonstrate the neural characteristics and spatial patterning of the epithelial tissue. We further show that the XEN cells differentiate reciprocally to a visceral endoderm-like state. Finally, we demonstrate that local inhibition of WNT signaling and production of a basement membrane by the XEN cells underlie the formation of the neuroepithelial tissue. In summary, we establish "XEN Enhanced Gastruloids" (XEGs) to explore heterotypic cellular interactions as a means to achieve complex, tissue-level organization in vitro.

developmental biology↗