Self-Organization and Symmetry Breaking in Human Embryo and Models
Event Details
- Type
- Monday Lecture Series
- Speaker(s)
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Ali Brivanlou, Ph.D., Robert and Harriet Heilbrunn Professor and head, Laboratory of Synthetic Embryology, The Rockefeller University
- Speaker bio(s)
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Gastrulation is one of the most significant aspects of our embryonic development, as it initiates the self-organization of germ layers and the emergence of the body axis by symmetry breaking events. Yet, understanding the principles of human gastrulation is essential not only to unveil human-specific traits but also for understanding developmental diseases and fertility challenges. We have developed human embryo models derived from human embryonic stem cells to explore gastrulation across molecular, cellular, and tissue scales. Upon in vitro attachment, we discovered that human blastocyst models (blastoids), as well as natural human embryos, initiate gastrulation at day 12, correcting previous assumptions (De Santis et al., 2024). To gain mechanistic insight into these crucial processes in human development, we designed a new optogenetic tool to control morphogen signaling in our gastrula models (gastruloids). Combined with defined geometry and engineered mechanical states, we demonstrated that symmetry breaking emerges from an interplay of a cascade of morphogens, initiated by BMP4, and mechanical force sensing via YAP1 (De Santis et al., 2025). In all, these studies establish a conceptual and experimental framework for understanding the cellular and molecular principles governing self-organization during human early development.
Ali Brivanlou has made revolutionary contributions to our current knowledge of early embryonic development. Originally, working with amphibian embryos, he solved the long-lasting molecular basis of neural induction originally articulated in the 1920’s. He demonstrated that neural fate requires the elimination of inhibitory TGFß signals. He coined this mechanism “The Default Model” of neural induction. While controversial at the beginning, the model was validated by the discovery of organizer-specific secreted TGFß inhibitors: Noggin, Chordin, and Follistatin. To address evolutionary conservation, Ali turned to early human embryology. He developed culture conditions that allowed blastocysts to attach in vitro and unveiled a remarkable degree of self-organization of germ layers during the second week of gestation, and the discovery of embryonic cell types previously not detected in model organisms. To model human embryos, he derived a collection of human embryonic stem cells (hESCs) from blastocyst, which contributed to the first NIH registry lines. With leaders in the stem cell field, he published the first international standards for quantitative and functional measurements of hESCs. In collaboration with Physics colleagues, he generated the first standardized human embryo models derived from hESCs cultured on microchips and demonstrated that geometrical confinement was sufficient to induce self-organization of germ layers in response to a single stimulus. This demonstrated the evolutionary conservation of the Default Model of neural induction in human embryo models. Additionally, the approach was used to model human-specific pediatric and neurological diseases. His seminal contributions now have a permanent home in current textbooks of Molecular and Developmental Biology, and Neurosciences. Ali Brivanlou has 200 publications, more than 30,000 citations. He is considered the father of the Default Model of neural induction.
- Open to
- Campus Only