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A new study shows that the hourglass model of embryonic development is visible not only at the level of whole embryos, but already within individual cell lineages. Researchers at the Max Planck Institute for Evolutionary Biology and Kiel University have demonstrated that cells from different species use particularly similar genetic programmes during the middle phase of development. This opens up a new perspective on how conserved developmental processes and species-specific differences arise.
To the point
• A classic developmental pattern resolved at cellular resolution: The study shows that the hourglass pattern, long observed across species, is embedded within individual cell lineages.
• Two complementary molecular signatures indicate broader conserved phase of development: Cells across species show the highest gene expression similarity at neurula stage and rely on evolutionarily ancient genes during pharyngula, defining an extended conserved period of embryogenesis.
• An asymmetric hourglass: Late developmental stages diverge more strongly than early stages, indicating that conservation progressively relaxes as embryos acquire species-specific traits.
Scientists have long observed that embryos of different species within a phylum look quite distinct at early and late developmental stages but resemble one another more during mid-embryogenesis, a phenomenon known as developmental hourglass.
In 2010, two seminal studies provided molecular evidence for this pattern. The group of Prof. Dr. Diethard Tautz at the Max Planck Institute for Evolutionary Biology in Plön showed that zebrafish embryos predominantly express evolutionarily ancient genes during mid-embryogenesis, while the group of Dr. Pavel Tomančák at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden demonstrated that gene expression programs are most similar across Drosophila species during this period.
The waist of hourglass is therefore considered a developmental phase that is particularly resistant to evolutionary change and indicates an onset of developmental divergence. However, most studies so far have examined entire embryos or large tissues.
“Yet embryonic development is not simply an embryo-level process. Embryogenesis is fundamentally driven by the behavior of individual cells, which divide, migrate, and specialize to build complex organisms.” says Dr. Markéta Kaucká, who led the study. “This opened an important question: does the hourglass reflect constraints acting across the entire embryo, or does the pattern emerge from the properties of individual cell lineages?”
In a new study published in Nature Communications, researchers from the Max Planck Institute for Evolutionary Biology and Kiel University investigated whether hourglass pattern can be observed at a much finer resolution than the entire organism, specifically within the cellular lineages that construct the embryo itself.
Mapping development at the cellular level
To determine whether the developmental hourglass operates at the level of individual cells, the researchers analyzed publicly available single-cell transcriptomic datasets from developing mouse and zebrafish, spanning multiple stages of embryogenesis. “To understand how cells progress through the development, we first reconstructed cellular trajectory maps. These maps resemble family trees of individual cells, capturing the relationships and transitions between cell states over time”, explains first author and recent PhD graduate Dr. Amor Damatac II. “This allowed us to follow molecular changes along individual cellular trajectories as development progresses.”
Tracking gene expression along these trajectories allowed the team to follow whether the same conserved developmental pattern previously observed only at the level of whole embryos is also present at the cellular level.
A cellular hourglass
Using the reconstructed cellular trajectories, the researchers next asked whether the defining signatures of the molecular hourglass could be detected within individual cell lineages. They examined two key hallmarks of the molecular hourglass: the degree of gene expression conservation between species and the evolutionary age of genes expressed during development.
The team found that cellular trajectories during vertebrate embryogenesis follow a striking hourglass-like pattern. During mid-embryogenesis, particularly around the neurula stage, cell states in mouse and zebrafish showed the highest similarity in gene expression, indicating strong conservation of developmental programs across species. At the same time, the researchers observed that during a slightly later stage known as the pharyngula stage, the majority of cell states expressed the evolutionarily oldest sets of genes, suggesting that deeply conserved genetic programs dominate this phase of development. These two molecular aspects form the unmatched waists of hourglass and show that vertebrate developmental conservation spans a broader phylotypic period rather than a single sharply defined stage.
Together, these results show that the developmental hourglass observed in whole embryos reflects a pattern embedded within individual cell lineages and emerging from their combined behavior.
An asymmetric hourglass
The study also uncovered an additional feature: late developmental stages diverge more strongly between species than early stages. This asymmetric hourglass suggests that evolutionary divergence intensifies during later development, as embryos acquire specialized structures and species-specific traits.
Why this discovery matters
The findings provide a new perspective on how embryos maintain robustness despite the enormous complexity of development. While cells progressively specialize to form different tissues and organs, mid-embryonic stages require convergence on shared gene-regulatory programs that ensure the body plan forms correctly.
With the rapid expansion of single-cell technologies, this cellular perspective may transform how scientists study developmental conservation and evolutionary divergence across multicellular life.
Dr. Markéta Kaucká
Max Planck Research Group Leader
Max Planck Institute for Evolutionary Biology
Max Planck Research Group Evolutionary Developmental Dynamics
Damatac, A., Ullrich, K.K., Klimovich, A. et al. A cellular basis for the hourglass pattern in vertebrate embryogenesis. Nat Commun 17, 2404 (2026). https://doi.org/10.1038/s41467-026-69828-9
Vertebrate embryogenesis follows a pattern known as the developmental hourglass. During mid-embryoge ...
Source: Markéta Kaucká
Copyright: MPI EvolBio
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