PHYSICS SEMINAR by Yusuf İlker Yaman

Embryonic development is among the most complex biological processes in nature. The intricate genetic and morphogenetic mechanisms that govern these highly coordinated events have been studied in various model organisms for decades, however, our understanding of human embryonic development remains lacking due to the inaccessibility and ethical problems. While recent advances in stem cell-based methodologies offer a means to dissect this complexity by recapitulating developmental processes in a Petri dish, their lack of reproducibility has impeded gaining mechanistic insights. In this talk, I will discuss our robust and reproducible model that recapitulates human spinal cord development through controlled symmetry breaking of spatially coupled organoids (1). The initial symmetry-breaking event in human development occurs through a critical process known as gastrulation for establishing the embryo's head-to-tail axis. The embryo elongates on this axis and gets sequentially and periodically segmented into discrete structures known as somites. Axial segmentation is directed by a symphony of spatiotemporally structured dynamic gene expression and signaling gradients. To study this complex process, we have recently developed a robust and reproducible human organoid model derived from pluripotent stem cells. Through inducing symmetry breaking by spatially coupling epithelial cysts, this model faithfully reproduces the key aspects of human axial morphogenesis, including axial elongation, neural tube formation, and the rhythmic, spatiotemporal waves of gene expression, culminating in periodic and sequential somite segmentation. Moreover, I will discuss the regulation of critical active matter properties of the cells through gene expression and cell signaling, which could illuminate the detailed physics underlying the morphogenesis of developing human embryos. By creating and experimenting with organoids that accurately mimic the developmental mechanisms and structural features of human embryos, our approach provides a potent avenue for unraveling the mechanisms that drive complex human developmental processes. 1- Cell, 2023, https://doi.org/10.1016/j.cell.2022.12.042