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Bruno C Vellutini#, Marina B Cuenca, Abhijeet Krishna, Alicja Szałapak, Carl D. Modes, Pavel Tomancak#
Patterned invagination prevents mechanical instability during gastrulation.
Nature, Art. No. doi: 10.1038/s41586-025-09480-3 (2025)
Open Access PubMed Source   

Mechanical forces are crucial for driving and shaping tissue morphogenesis during embryonic development1-3. However, their relevance for the evolution of development remains poorly understood4. Here we show that an evolutionary novelty of fly embryos-the patterned embryonic invagination known as the cephalic furrow5-7-has a mechanical role during Drosophila gastrulation. By integrating in vivo experiments and in silico simulations, we demonstrate that the head-trunk boundary of the embryo is under increased compressive stress due to the concurrent formation of mitotic domains and germ band extension and that the cephalic furrow counteracts these stresses, preventing mechanical instabilities during gastrulation. Then, by comparing the genetic patterning of species with and without the cephalic furrow, we find evidence that changes in the expression of the transcription factor buttonhead are associated with the evolution of the cephalic furrow. These results suggest that the cephalic furrow may have evolved through the genetic stabilization of morphogenesis in response to the mechanical challenges of dipteran gastrulation. Together, our findings uncover empirical evidence for how mechanical forces can influence the evolution of morphogenetic innovations in early development.
@article{Vellutini9040,
author={Bruno C Vellutini, Marina B Cuenca, Abhijeet Krishna, Alicja Szałapak, Carl D. Modes, Pavel Tomancak},
title={Patterned invagination prevents mechanical instability during gastrulation.},
journal ={Nature},
volume={},
pages={1--1},
year=2025
}

Jannik Rothkegel, Sylvia Kaufmann, Michaela Wilsch-Bräuninger, Catarina Lopes, Rita Mateus
Purine Molecular Interactions Determine Anisotropic Shape of Zebrafish Biogenic Crystals.
Small Methods, Art. No. doi: 10.1002/smtd.202401956 (2025)
Open Access PubMed Source   

Across phyla, many organisms self-organize crystals, for functions like vision, pigmentation, and metabolite storage. In zebrafish, a vertebrate known for its crystal-based color patterns, iridophores concentrate purines in membrane-bound organelles, the iridosomes. Inside these vesicles, crystals assemble into large, flat, and thin hexagons following unknown mechanisms that defy typical thermodynamic interactions. Here, we investigate the development of zebrafish iridosomal crystals by using live imaging, cryoFIB-SEM, and novel morphometric analysis pipelines. In doing so, we find that crystal growth predominantly occurs along the b-crystallographic axis, producing their characteristic anisotropic shape. By performing comparative genetic analyses in vivo and reproducing such conditions in silico, we uncover that the zebrafish crystals' in-plane hydrogen bond molecular structure is the main determinant for the observed crystal anisotropy. Macroscopically, the b-axis anisotropy is controlled by the ratio of guanine-to-hypoxanthine in the iridosome, without affecting the other axes. At the atomic level, the extent of the (100) facet anisotropy depends entirely on the type, number, and strength of molecular H-bonds within the crystal lattice. Mechanistically, our work shows that purine diversity and availability inside the zebrafish iridosome is key to form an anisotropic crystal lattice, leading to the observed functional crystal shapes.
@article{Rothkegel9038,
author={Jannik Rothkegel, Sylvia Kaufmann, Michaela Wilsch-Bräuninger, Catarina Lopes, Rita Mateus},
title={Purine Molecular Interactions Determine Anisotropic Shape of Zebrafish Biogenic Crystals.},
journal ={Small methods},
volume={},
pages={1--1},
year=2025
}

Anaïs Bailles#, Giulia Serafini, Heino Andreas, Christoph Zechner, Carl D. Modes, Pavel Tomancak#
Anisotropic stretch biases the self-organization of actin fibers in multicellular Hydra aggregates.
Proc Natl Acad Sci U.S.A., 122(32) Art. No. e2423437122 (2025)
Open Access PubMed Source   

During development, groups of cells generate shape by coordinating their mechanical properties through an interplay of self-organization and prepatterning. Hydra displays a striking planar pattern of actin fibers at the organism scale, and mechanics influence the morphogenesis of biological structures during its prepatterned regeneration. However, how mechanics participate in the formation of an ordered pattern from a totally disordered state remains unknown. To study this, we used cellular aggregates formed from dissociated Hydra cells, which initially lose all actin polarity yet regenerate a long-range actin pattern. We showed quantitatively that the actin meshwork evolves from a disordered symmetric state to an ordered state in which rotational symmetry is broken, and translation symmetry is partially broken, with the nematic and smectic order parameters increasing over days. During the first hours, the actin meshwork displayed spatial heterogeneity in the nematic order parameter, and ordered domains separated by line defects progressively grew and fused. This suggests that local cell-cell interactions drive the transition from disorder to order. To understand the mechanism of ordering, we perturbed the tissue's physical constraints. We showed that while topology and geometry do not have a direct effect, anisotropic stretch biases the emerging orientation of the actin meshwork within hours. Surprisingly, although a Wnt head organizer is expected to play a role in the actin ordering, the stretch-associated alignment happened without the prior formation of a head organizer. This demonstrates the role of tissue mechanics in the alignment of the actin fibers during the disorder-to-order transition.
@article{Bailles9036,
author={Anaïs Bailles, Giulia Serafini, Heino Andreas, Christoph Zechner, Carl D. Modes, Pavel Tomancak},
title={Anisotropic stretch biases the self-organization of actin fibers in multicellular Hydra aggregates.},
journal ={Proceedings of the National Academy of Sciences of the United States of America},
volume={122},
issue ={32},
pages={null--null},
year=2025
}

Lucas Ribas, Rita Mateus
Start-Shape-Stop: Cell communication mechanisms controlling organ size.
Semin Cell Dev Biol, 174 Art. No. 103641 (2025)
Open Access PubMed Source   

Accurate growth control is critical for the achievement of proportional organs during animal development and repair processes. Either extra or deficient growth rates lead to organ functional impairment. The understanding of how organs acquire, recover, and fine-tune their final size has been a long-lasting biological problem. How do organs measure their current size? This review is centered on this question through the lens of the physical properties governing cell communication mechanisms. In particular, we highlight and discuss new insight into the dynamic connections between several cellular control mechanisms that operate at different timescales to regulate organ growth and morphogenesis.
@article{Ribas9039,
author={Lucas Ribas, Rita Mateus},
title={Start-Shape-Stop: Cell communication mechanisms controlling organ size.},
journal ={Seminars in cell & developmental biology},
volume={174},
pages={null--null},
year=2025
}

Anna Dowbaj, Aleksandra Sljukic, Armin Niksic, Cedric Landerer, Julien Delpierre, Haochen Yang, Aparajita Lahree, Ariane C Kühn, David Beers, Helen M Byrne, Sarah Seifert, Heather A Harrington, Marino Zerial, Meritxell Huch
Mouse liver assembloids model periportal architecture and biliary fibrosis.
Nature, 644(8076) 473-482 (2025)
Open Access PubMed Source Full Text   

Modelling liver disease in vitro requires systems that replicate disease progression1,2. Current tissue-derived organoids do not reproduce the complex cellular composition and tissue architecture observed in vivo3. Here, we describe a multicellular organoid system composed of adult hepatocytes, cholangiocytes and mesenchymal cells that recapitulates the architecture of the liver periportal region and, when manipulated, models aspects of cholestatic injury and biliary fibrosis. We first generate reproducible hepatocyte organoids with a functional bile canaliculi network that retain morphological features of in vivo tissue. By combining these with cholangiocytes and portal fibroblasts, we generate assembloids that mimic the cellular interactions of the periportal region. Assembloids are functional, consistently draining bile from bile canaliculi into the bile duct. Of note, manipulating the relative number of portal mesenchymal cells is sufficient to induce a fibrotic-like state, independently of an immune compartment. By generating chimeric assembloids of mutant and wild-type cells, or after gene knockdown, we show proof of concept that our system is amenable to investigating gene function and cell-autonomous mechanisms. Together, we demonstrate that liver assembloids represent a suitable in vitro system to study bile canaliculi formation, bile drainage and how different cell types contribute to cholestatic disease and biliary fibrosis in an all-in-one model.
@article{Dowbaj9003,
author={Anna Dowbaj, Aleksandra Sljukic, Armin Niksic, Cedric Landerer, Julien Delpierre, Haochen Yang, Aparajita Lahree, Ariane C Kühn, David Beers, Helen M Byrne, Sarah Seifert, Heather A Harrington, Marino Zerial, Meritxell Huch},
title={Mouse liver assembloids model periportal architecture and biliary fibrosis.},
journal ={Nature},
volume={644},
issue ={8076},
pages={473--482},
year=2025
}

Woorin Kim#, Nicola Schmidt, Matthias Jost, Elijah Mbandi Mkala, Sylke Winkler, Guangwan Hu, Tony Heitkam#, Stefan Wanke#
Diverging repeatomes in holoparasitic Hydnoraceae uncover a playground of genome evolution.
New Phytol, 247(3) 1520-1537 (2025)
Open Access PubMed Source   

The transition from an autotrophic to a heterotrophic lifestyle is associated with numerous genomic changes. These often involve large genomic alterations, potentially driven by repetitive DNAs. Despite their recognized role in shaping plant genomes, the contribution of repetitive DNAs to parasitic plant genome evolution remains largely unexplored. This study presents the first analysis of repetitive DNAs in Hydnoraceae genomes, a plant family whose members are holoparasitic. Repetitive DNAs were identified and annotated de novo. Abundant transposable elements and 35S ribosomal DNA in the Hydnora visseri genome were reconstructed in silico. Their patterns of abundance and presence-absence were individually and comparatively analyzed. Both Hydnoraceae genera, Hydnora and Prosopanche, exhibit distinct repeatome profiles which challenge our current understanding of repeatome and rDNA evolution. The Hydnora genomes are dominated by long terminal repeat retrotransposons, while the Prosopanche genomes vary greatly in their repeat composition: Prosopanche bonacinae with a highly abundant single DNA transposon and Prosopanche panguanensis with over 15% 5S rDNA, compared to ≤ 0.1% in the Hydnora genomes. The repeat profiles align with the phylogeny, geographical distribution, and host shifts of the Hydnoraceae, indicating a potential role of repetitive DNAs in shaping Hydnoraceae genomes to adapt to the parasitic lifestyle.
@article{Kim9014,
author={Woorin Kim, Nicola Schmidt, Matthias Jost, Elijah Mbandi Mkala, Sylke Winkler, Guangwan Hu, Tony Heitkam, Stefan Wanke},
title={Diverging repeatomes in holoparasitic Hydnoraceae uncover a playground of genome evolution.},
journal ={The New phytologist},
volume={247},
issue ={3},
pages={1520--1537},
year=2025
}

Anna Hadarovich, David Kuster, Maria Luisa Romero Romero, Agnes Toth-Petroczy
On the Evolution of Biomolecular Condensates: From Prebiotic Origins to Subcellular Diversity.
Annu Rev Cell Dev Biol, Art. No. doi: 10.1146/annurev-cellbio-101123-051723 (2025)
PubMed Source   

Biomolecular condensates provide a way to compartmentalize subcellular components with high temporal and spatial resolution, enabling rapid responses to signals and environmental changes. While the formation, components, and function of some condensates are well-characterized, their presence across organisms, their evolutionary history, and their origin are less well-understood. Here, we review the diversity of condensate components and highlight that not only disordered but also fully structured proteins are capable of driving condensate formation. We compare how proteomes of condensates overlap within and across species, and we present functionally analogous condensates across organisms. Additionally, we discuss the potential role of condensation in early life, suggesting that phase separation could have facilitated the selection and concentration of prebiotic molecules, promoting essential biochemical processes. We conclude that condensate-related organization principles are ubiquitously used across organisms from bacteria to mammals, and they potentially played a key role in prebiotic evolution, serving as primitive compartments for early biochemical processes.
@article{Hadarovich9033,
author={Anna Hadarovich, David Kuster, Maria Luisa Romero Romero, Agnes Toth-Petroczy},
title={On the Evolution of Biomolecular Condensates: From Prebiotic Origins to Subcellular Diversity.},
journal ={Annual review of cell and developmental biology},
volume={},
pages={1--1},
year=2025
}

Xiao Yan, David Kuster, Priyesh Mohanty, Jik Nijssen, Karina Pombo-García, Jorge Garcia Morato, Azamat Rizuan, Titus Franzmann, Aleksandra Sergeeva, Anh M Ly, Feilin Liu, Patricia M Passos, Leah George, Szu-Huan Wang, Jayakrishna Shenoy, Helen L Danielson, Busra Ozguney, Alf Honigmann, Yuna M Ayala, Nicolas L Fawzi, Dennis W Dickson, Wilfried Rossoll, Jeetain Mittal#, Simon Alberti#, Anthony Hyman#
Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates.
Cell, 188(15) 4123-4140 (2025)
Open Access PubMed Source   

Cytosolic aggregation of the nuclear protein TAR DNA-binding protein 43 (TDP-43) is associated with many neurodegenerative diseases, but the triggers for TDP-43 aggregation are still debated. Here, we demonstrate that TDP-43 aggregation requires a double event. One is up-concentration in stress granules beyond a threshold, and the other is oxidative stress. These two events collectively induce intra-condensate demixing, giving rise to a dynamic TDP-43-enriched phase within stress granules, which subsequently transition into pathological aggregates. Intra-condensate demixing of TDP-43 is observed in iPS-motor neurons, a disease mouse model, and patient samples. Mechanistically, intra-condensate demixing is triggered by local unfolding of the RRM1 domain for intermolecular disulfide bond formation and by increased hydrophobic patch interactions in the C-terminal domain. By engineering TDP-43 variants resistant to intra-condensate demixing, we successfully eliminate pathological TDP-43 aggregates in cells. We suggest that up-concentration inside condensates followed by intra-condensate demixing could be a general pathway for protein aggregation.
@article{Yan9005,
author={Xiao Yan, David Kuster, Priyesh Mohanty, Jik Nijssen, Karina Pombo-García, Jorge Garcia Morato, Azamat Rizuan, Titus Franzmann, Aleksandra Sergeeva, Anh M Ly, Feilin Liu, Patricia M Passos, Leah George, Szu-Huan Wang, Jayakrishna Shenoy, Helen L Danielson, Busra Ozguney, Alf Honigmann, Yuna M Ayala, Nicolas L Fawzi, Dennis W Dickson, Wilfried Rossoll, Jeetain Mittal, Simon Alberti, Anthony Hyman},
title={Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates.},
journal ={Cell},
volume={188},
issue ={15},
pages={4123--4140},
year=2025
}

Rudrarup Bose, Daniele Rossetto, Anju Tomar, Sanguen Lee, Sheref S Mansy, T-Y Dora Tang
Protometabolically Generated NADH Mediates Material Properties of Aqueous Dispersions to Coacervate Microdroplets.
Biomacromolecules, Art. No. doi: 10.1021/acs.biomac.5c00349 (2025)
Open Access PubMed Source   

Macromolecular assembly between biomolecules dictates the material state of chemically complex aqueous dispersions such as the cytoplasm. The formation of protein precipitates, fibers, or liquid droplets have been associated with metabolic regulation and disease. However, the effect of metabolic flux on the material properties of aqueous dispersions remains underexplored. Here, we use the protometabolic reduction of NAD+ to NADH by pyruvate to study the effect of NADH production on the phase separation properties of polyarginine. We show that reduction of NAD+ in the presence of polyarginine can tune the material properties of the dispersion between precipitates, homogeneous solution, and liquid droplets depending on the buffer concentration. In situ droplet formation results in 2-3 times higher reaction rate and NADH yield, compared to homogeneous solution. Our study provides a setting for coupling protometabolism to active protocell environments in the absence of enzymes and sheds light on the self-regulation of metabolic flux on mediating biomolecular phase separation.
@article{Bose9025,
author={Rudrarup Bose, Daniele Rossetto, Anju Tomar, Sanguen Lee, Sheref S Mansy, T-Y Dora Tang},
title={Protometabolically Generated NADH Mediates Material Properties of Aqueous Dispersions to Coacervate Microdroplets.},
journal ={Biomacromolecules},
volume={},
pages={1--1},
year=2025
}

David Grommisch*, Evelien Eenjes*, Maeve L Troost, Maria Genander
Epithelial architecture and signaling activity in the adult human esophagus.
Front Cell Dev Biol, 13 Art. No. 1632255 (2025)
Open Access PubMed Source   

Barrier epithelia function to shield the inside of our bodies from external stressors and pathogens. The esophageal epithelium is no exception, providing protection while at the same time transporting food to the stomach. Although many epithelial tissues are comparable between humans and mice, the human esophageal epithelium displays unique features in both progenitor cell organization and tissue architecture compared to the mouse. These differences have limited our understanding of the adult human esophagus, hindering the development of therapeutic strategies targeting human esophageal disease. Herein, we contrast the esophageal epithelial architecture and progenitor cell populations in mice and humans and discuss the role of a tentative human-specific progenitor cell population located in the submucosal gland ducts. Furthermore, we review current models available to study the human esophageal epithelium, focusing predominantly on adult primary organoids and epithelioids as well as the generation of human developmental esophageal epithelial cells from induced pluripotent stem cells. Finally, we discuss signaling activity implicated in maintaining normal human epithelial homeostasis, and how these pathways contribute to disease development. We aim to provide a comprehensive outlook on our current understanding of the human esophageal epithelium, while simultaneously highlighting unanswered questions in esophageal epithelial maintenance.
@article{Grommisch9034,
author={David Grommisch, Evelien Eenjes, Maeve L Troost, Maria Genander},
title={Epithelial architecture and signaling activity in the adult human esophagus.},
journal ={Frontiers in cell and developmental biology},
volume={13},
pages={null--null},
year=2025
}
* joint first authors, # joint corresponding authors