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External seminar: Thomas Gregor

When Mar 18, 2024
from 11:00 to 12:00
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External seminar: Thomas Gregor (Institut Pasteur, Paris)

"Precise and scalable self-organization in mammalian pseudo-embryos"

Host: Samir Merabet

Gene expression is an intrinsically noisy process. However, the body plans across individuals of a given species result in precise and reproducible spatial patterns. The transformation of variability in transcriptional activity into reproducible and precise gene expression patterns has been demonstrated in animal models ranging from worms to vertebrates. In flies, for example, the precision of the macroscopic features of the body plan has been traced back to the fundamental limits of molecular noise set by physical principles. The spatial accuracy of these features is proportional to system size and sufficient to distinguish individual cells from their neighbors. However, we know little about such accuracy in mammalian development. Mammals are different, and patterning and gene regulation are thought to be more variable. I will present an overview of my lab's previous contributions to the above findings and then introduce our recent use of a novel in vitro model called “gastruloids” to revisit these questions in mammalian development. We demonstrate an intrinsic reproducibility of the self-organizing anteroposterior body axis in gastruloids, both for growth dynamics and gene expression patterns. The system exerts tight control over expression levels and positions pattern boundaries with single-cell precision. Gastruloid growth scales with the initial number of seed cells, and gene expression patterns scale precisely with system size. Our results reveal developmental precision, reproducibility, and size-scaling for a mammalian system that, unlike a fly embryo, is not constrained by fixed boundary conditions (i.e., an eggshell). Gastruloids develop in an artificial context where boundaries are created through spontaneous self-organization. No selection pressure has acted on the system for it to operate at such high levels of precision. These spontaneously emerging quantitative properties could thus be fundamental features of multicellularity, reaching across half a billion years of evolutionary change.

Monday, March 18th

Amphi I