How Embryos Suspend Development to Survive
In the hidden world of early development, scientists are uncovering one of nature's most astonishing survival strategies.
Imagine putting life on pause—not in science fiction, but in reality. For dozens of mammal species, from tiny mice to majestic kangaroos, this is not just possible; it's a fundamental survival strategy known as embryonic diapause. This remarkable phenomenon allows a developing embryo to temporarily suspend its development, waiting for the right moment to continue its journey toward birth.
For years, this biological mystery puzzled scientists. How could something as complex as a developing embryo simply halt its progression, then restart flawlessly? Today, researchers like Dr. Aydan Bulut-Karslioglu are uncovering the molecular secrets behind this extraordinary process, revealing insights that could reshape our understanding of development, stem cells, and even potential medical applications.
Embryonic diapause represents one of nature's most elegant solutions to environmental challenges. It's a reversible state of suspended animation that gives embryos extra time to develop, significantly increasing their chances of survival 4 . Think of it as nature's way of ensuring that offspring are born when conditions are optimal—when food is abundant, temperatures are favorable, or previous siblings have been weaned.
Species of mammals exhibit embryonic diapause
Reversible process with no developmental defects
Maximum recorded duration of diapause in some species
This phenomenon occurs across the animal kingdom, from over 130 species of mammals to various insects and fish. What makes it particularly fascinating to scientists is its perfect reversibility—the embryo can pause for days, weeks, or even months, then resume development normally once conditions improve.
"Our research focuses on the epigenetic and metabolic mechanisms regulating embryonic development" 1 .
For Dr. Bulut-Karslioglu, a Group Leader at the Max Planck Institute for Molecular Genetics, diapause represents more than just a biological curiosity. Her work has positioned her at the forefront of this emerging field, earning her prestigious recognition including Development's Outstanding Paper Prize for 2022 and a European Research Council Starting Grant for 2023 1 .
Dr. Bulut-Karslioglu's scientific journey is as fascinating as her research. She began her academic path in chemical engineering before shifting focus to molecular biology for her Master's degree 1 . This interdisciplinary background likely equipped her with the unique perspective needed to tackle complex biological problems.
Started academic path in chemical engineering before transitioning to molecular biology
Completed doctoral research in Thomas Jenuwein's lab, focusing on epigenetics
Conducted postdoctoral research at University of California, San Francisco
Received award allowing her to establish independent research lab in Berlin
Awarded European Research Council Starting Grant for her groundbreaking work
Honored by German Stem Cell Network for research on stem cell state transitions
The scientific community has taken note of her groundbreaking work. Most recently, in 2025, she was honored with the GSCN Young Investigator Award from the German Stem Cell Network for her research on mechanisms regulating stem cell state transitions and fate commitment 4 .
"Networks like the GSCN help scientists with a shared passion come together and consolidate efforts to move the field forward. I am very proud to be honored with this prize that recognizes our team's work on breaking new ground in the biology of dormancy" 4 .
One of the most significant discoveries from Dr. Bulut-Karslioglu's research came during her postdoctoral work at UCSF, where she identified mTOR as a crucial regulator of developmental timing in mouse embryos 4 .
The mTOR pathway acts as a central hub in cells, integrating signals about nutrient availability, energy levels, and environmental conditions. When conditions are unfavorable, dialing down mTOR activity essentially flips the "pause switch" in the embryo.
So how did researchers uncover this mechanism? The experimental approach provides a fascinating glimpse into scientific discovery:
Scientists first compared actively developing embryos with those in diapause, looking for differences in gene expression, metabolic activity, and epigenetic markers.
Through systematic testing of various signaling pathways, the mTOR (mechanistic target of rapamycin) pathway emerged as a key difference between the two states.
Researchers then experimentally inhibited mTOR activity in developing embryos and found they could induce a diapause-like state even without environmental triggers.
The reverse was also tested—by reactivating mTOR signaling in paused embryos, scientists could restart development, confirming mTOR's central role.
| Aspect | Normal Development | Diapause State |
|---|---|---|
| mTOR Activity | High | Significantly reduced |
| Metabolic Rate | High | Dramatically lowered |
| Gene Expression | Active developmental program | Distinct pausing signature |
| Epigenetic State | Dynamic changes | Stable, maintained pattern |
| Cellular Division | Active | Temporarily halted |
What makes Dr. Bulut-Karslioglu's research particularly groundbreaking is her focus on the epigenetic regulation of diapause 1 . While the genetic code itself remains unchanged during diapause, how that code is "read" undergoes significant shifts.
Epigenetic modifications act like molecular bookmarks, telling cellular machinery which genes to activate and which to ignore. During diapause, specific epigenetic marks help maintain the embryo in its paused state while preserving its potential to resume normal development.
This epigenetic dimension explains how the embryo can maintain its developmental potential despite the dramatic slowdown in cellular activity. The "blueprint" for development remains intact, just temporarily inaccessible.
| Epigenetic Marker | Role in Normal Development | Modification During Diapause |
|---|---|---|
| DNA Methylation | Regulates gene expression patterns | Specific genes important for development are protected from methylation changes |
| Histone Modifications | Control DNA accessibility | Distinct modification patterns that maintain developmental genes in a "poised" state |
| Chromatin Structure | Determines 3D organization of DNA | Reorganized to maintain key developmental programs in a repressed but ready state |
| Tool/Method | Function in Diapause Research |
|---|---|
| Single-cell RNA-sequencing | Measures gene expression in individual cells, revealing heterogeneity in diapausing embryos |
| Quantitative Imaging | Tracks cellular and molecular changes over time with precise measurements |
| Machine Learning Segmentation | Automates analysis of complex image data, identifying patterns difficult for humans to detect |
| Epigenetic Profiling | Maps modifications to DNA and histones that regulate gene expression without changing DNA sequence |
| Metabolic Flux Analysis | Tracks how nutrients and energy are utilized and redirected during the diapause transition |
| Optogenetics | Uses light to control specific signaling pathways with high precision in space and time |
This interdisciplinary approach brings together biology, physics, and computational methods to understand state transitions in biological systems 3 .
The implications of understanding embryonic diapause extend far beyond satisfying scientific curiosity. As Dr. Bulut-Karslioglu's team's "additional work on oxygen sensing showed the extent to which stem cell fate decisions are influenced by the cellular environment" 4 , these findings have potentially broad applications:
Diapause embryos display remarkable similarities to stem cells in a quiescent state. Understanding how embryonic cells maintain their developmental potential while paused could help improve stem cell therapies and tissue engineering.
Understanding the molecular signals that control embryonic development could lead to improvements in IVF technologies and fertility preservation.
The parallels between dormant embryos and dormant cancer cells—both capable of reactivating after extended periods—are striking. Lessons from diapause might inform new approaches to preventing cancer recurrence.
If we can understand how embryos reversibly slow their metabolism without damage, we might apply similar principles to improve organ preservation for transplantation.
The study of transitions in biological systems represents an exciting frontier in science. As highlighted by the upcoming EMBL course, the field is moving toward integrating "biological physics and morphogenesis" 3 and exploring "fundamental principles of collective animal behaviour" 3 across scales.
Dr. Bulut-Karslioglu's recent ERC Proof of Concept Grant awarded in 2025 4 suggests her lab continues to break new ground. The recognition from the German Stem Cell Network specifically acknowledges her work on "stem cell state transitions and fate commitment" 4 , indicating these findings may have significant implications for stem cell biology.
Embryonic diapause represents one of nature's most elegant solutions to environmental uncertainty. Through the dedicated work of scientists like Dr. Aydan Bulut-Karslioglu, we're beginning to understand the sophisticated molecular machinery that makes this biological miracle possible.
The discovery of mTOR's central role, coupled with insights into epigenetic regulation, reveals a complex system honed by evolution to ensure survival against unpredictable odds. As research continues to bridge biological scales and integrate diverse disciplines, we move closer to not only understanding these remarkable transitions but potentially harnessing their principles for human health and medicine.
In the words of one researcher who attended a course on developmental transitions, this interdisciplinary approach represents "the future of Developmental Biology" 3 —a future where physics, computation, and biology converge to unravel life's deepest mysteries, including how and why development sometimes hits the pause button.