@article{21860, abstract = {Glutamate excitotoxicity is a cell death mechanism triggered by accumulation of glutamate in the extracellular space. The α-ketoglutarate dehydrogenase complex (αKGDHC), an enzyme of the tricarboxylic acid cycle, represents a branching point controlling glutamate formation and its consumption as a fuel. Hence, modulation of the activity of αKGDHC might alter the amount of glutamate available for excitotoxic effects. To address this hypothesis, hippocampal neurons in primary co-culture with glial cells were exposed to zero-Mg2 buffer to elicit excitotoxicity through N-methyl-D-aspartic acid (NMDA) receptor disinhibition. Pretreatment of the cultures with succinyl phosphonate, to inhibit αKGDHC, enhanced excitotoxity, whereas promotion of αKGDHC activity by pretreatment with thiamine caused an opposite action. Moreover, NMDA receptor currents – but not those mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors – were potentiated in neurons with impaired αKGDHC activity and diminished in neurons with boosted αKGDHC activity. The sensitization of NMDA receptors involved mGluR1 activation and was accompanied by enhanced neuronal discharge activity, elevated basal cytosolic Ca2+ levels, and augmented Ca2+ responses evoked by glutamate application. These results suggest that mGluR1-mediated potentiation of NMDA receptors contributes to a mechanism by which inhibition of αKGDHC might exacerbate glutamate excitotoxicity.}, author = {Goeschl, Vanessa and Hotka, Matej and Hochreiter, Bernhard and Hilber, Karlheinz and Boehm, Stefan and Kozlov, Andrey V. and Kubista, Helmut}, issn = {1477-9137}, journal = {Journal of Cell Science}, number = {8}, publisher = {The Company of Biologists}, title = {{α-ketoglutarate dehydrogenase complex activity modulates glutamate excitotoxicity via metabotropic regulation of NMDA receptors in primary cultures}}, doi = {10.1242/jcs.264420}, volume = {139}, year = {2026}, } @article{22301, abstract = {Auxin, primarily indole-3-acetic acid (IAA), is a central regulator of growth and development in land plants, but its physiological role in chlorophyte algae remains unclear. Here, we show that exogenous IAA modulates growth in Chlorella sorokiniana, Chlorella variabilis, and Chlamydomonas reinhardtii in a concentration-dependent manner. Low IAA concentrations promoted growth by accelerating the onset of cell division without affecting cell size, whereas higher concentrations inhibited proliferation. Radiotracer assays showed that all three species take up and release IAA across the plasma membrane through a combination of passive diffusion and energy-dependent, saturable processes. Competition by excess unlabeled natural and synthetic auxins further supported the presence of carrier-mediated transport with broad substrate recognition. Phylogenetic analyses identified potential PIN-like auxin exporters in chlorophytes and other non-plant eukaryotes, and structural modeling supported conservation of the overall PIN fold and predicted auxin-binding residues. However, functional assays in Xenopus laevis oocytes, tobacco BY-2 cultured cells, and Arabidopsis thaliana did not support a role for these proteins in directional auxin export. Instead, non-plant PIN homologs localized predominantly to the endoplasmic reticulum and showed limited or no transport activity in heterologous systems. Together, these findings indicate that auxin responsiveness and basic cellular auxin transport predate canonical PIN-mediated directional auxin export, which appears to be a later innovation of the streptophyte lineage.}, author = {Smoljan, Adrijana and Koutnik‐Abele, Sarah and Vladimirtsev, Dmitrii and Klíma, Petr and Bírošíková, Anita and Zhang, Yuzhou and Merrin, Jack and Schuster, Maximilian and Kurtović, Katarina and Hammes, Ulrich Z. and Petrášek, Jan and Friml, Jiří}, issn = {1744-7909}, journal = {Journal of Integrative Plant Biology}, publisher = {Wiley}, title = {{Auxin response and PIN‐mediated transport in chlorophyte algae}}, doi = {10.1111/jipb.70309}, year = {2026}, } @article{21883, abstract = {Three-dimensional (3D) printing has rapidly developed from a niche hobbyist activity into a widely accessible and indispensable technology across multiple scientific disciplines. Within microscopy, optical engineering laboratories and imaging core facilities, 3D printing enables creating customised solutions for sample holders, optical components and everyday laboratory tools that traditionally required specialised machining. By providing rapid prototyping, low-cost production and reproducibility, 3D printing facilitates innovation and efficiency in facility operations. This article provides a perspective on the possibilities, challenges, and practical aspects of implementing 3D printing within microscopy core facilities. Instead of providing technical review about 3D printing, we focus on service organisation, user engagement, resource management and community-driven repositories for design dissemination. Our aim is to share insights with those considering the implementation of 3D printing as a service for developing add-on components to ease the operation of different aspects of the machine-park driven services and those who are managing advanced instrumentation within research groups.}, author = {Goudarzi, Mohammad and Schuster, Maximilian and Milberger, Arthur and Gunkel, Manuel and Terjung, Stefan and Krens, Gabriel}, issn = {1365-2818}, journal = {Journal of Microscopy}, number = {3}, pages = {382--395}, publisher = {Wiley}, title = {{3D printing in core facilities – Low pain, high gain}}, doi = {10.1111/jmi.70106}, volume = {302}, year = {2026}, } @article{22608, abstract = {For tissues to spread, they must deform while staying intact. How spreading tissues balance flexibility with integrity is not yet well understood. Here, we show that keratin intermediate filaments adapt tissue mechanical resilience to the stresses arising in epithelial tissues during spreading. By analyzing the expansion of the enveloping cell layer (EVL) over the yolk cell in zebrafish embryos in vivo, we find that keratin network maturation in EVL cells is promoted by stresses building up within the spreading tissue. Through genetic interference and tissue rheology experiments, complemented by a vertex model with mechanochemical feedback, we demonstrate that stress-induced keratin network maturation in the EVL increases tissue viscosity, to prevent tissue rupture. Further, keratins are required in the yolk cell for mechanosensitive actomyosin network contraction and flow, the forces pulling the EVL. These dual mechanosensitive functions of keratins enable a balance between pulling force production and EVL mechanical resilience, ensuring uniform and robust tissue spreading.}, author = {Naik, Suyash and Keta, Yann-Edwin and Pranjic-Ferscha, Kornelija and Hannezo, Edouard B and Henkes, Silke and Heisenberg, Carl-Philipp J}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Keratins coordinate tissue spreading by balancing spreading forces with tissue material properties}}, doi = {10.1038/s41467-026-72366-z}, volume = {17}, year = {2026}, } @article{22295, abstract = {Despite the functional diversity of over 100 causal genes1,2,3, phenotypic convergence across models may reveal common neurobiological processes in autism spectrum disorder (ASD). Here we profiled 251 samples from 11 monogenic mouse models of ASD using single-nucleus multi-omic sequencing across three developmental stages, both sexes and two brain regions. Despite genetic heterogeneity, ASD-linked mutations converged on perturbations of the radial glial cell lineage. These alterations reflect a transient developmental delay rather than lasting lineage misspecification and resolve by postnatal stages. Molecularly, the largest transcriptional differences emerged in neurons at early postnatal stages. These changes included downregulation of synaptic and ion channel-related genes, consistent with homeostatic adaptation or delayed maturation. Network analysis showed molecular convergence across models within each developmental stage, suggesting that diverse mutations linked to ASD impinge on common, stage-specific processes. Convergence becomes less pronounced by postnatal day 14, highlighting the dynamic nature of ASD-associated changes. Cross-genotype heterogeneity is superimposed on stage-specific effects. Electrophysiology corroborated this pattern: mutants generally showed altered neuronal excitability and synaptic properties with model-specific nuances. Our study also highlighted sex-specific gene expression alterations, with female mice often displaying larger effect sizes than male mice. Together, our findings provide a comprehensive view of developmental cellular and molecular dynamics across models of ASD.}, author = {Schwarz, Lena A and Dotter, Christoph and Isaev, Sergey and Lisi, Michela and Malzl, Daniel and Büschl, Christoph and Ladstätter, Sabrina and Oliveira, Bárbara and Barel, Matteo and Basilico, Bernadette and Chintaluri, Chaitanya and Gorkiewicz, Sarah and Goudarzi, Mohammad and Belinova, Tereza and Reichl, Stephan and Sendžikaitė, Gintarė and Arcot Jayaram, Satish and Koppensteiner, Peter and Sommer, Christoph M and Vogels, Tim P and Menche, Jörg and Adameyko, Igor and Kharchenko, Peter Vasili and Bock, Christoph and Novarino, Gaia}, issn = {1476-4687}, journal = {Nature}, publisher = {Springer Nature}, title = {{Cortical development dynamics across autism spectrum disorder mouse models}}, doi = {10.1038/s41586-026-10679-1}, year = {2026}, } @inbook{22925, abstract = {Hybridization Chain Reaction (HCR) enables highly sensitive and multiplexed detection of mRNA with subcellular spatial resolution. It employs fluorophore-tagged DNA hairpins that self-assemble on target-bound probe pairs, amplifying the signal without enzymatic reactions. Here, we describe a protocol for performing HCR fluorescence in situ hybridization (FISH) on Xenopus tissue sections. We also outline a semi-automated image analysis pipeline that enables per-cell quantification of probe expression and co-localization. This method provides a robust and quantitative approach for visualizing gene expression patterns in situ.}, author = {Vijatovic, David and Papadopoulos, Stavros and Dalla Vecchia, Marco and Sweeney, Lora Beatrice Jaeger}, booktitle = {Xenopus}, editor = {Beck, Caroline W.}, issn = {1940-6029}, keywords = {mRNA FISH, Hybridization chain reaction, In situ hybridization, Fluorescence microscopy}, pages = {245--259}, publisher = {Springer}, title = {{Fluorescent in situ mRNA hybridization (FISH) using Hybridization Chain Reaction (HCR) in Xenopus cryosections}}, doi = {10.1007/978-1-0716-5360-9_11}, volume = {3049}, year = {2026}, } @article{23148, abstract = {Presenilin-1 (PS1) is an endoplasmic reticulum protein, most known for its role in pathogenesis of familial Alzheimer’s Disease (AD). PS1 has been attributed roles in intracellular calcium homeostasis in the brain, as well as in the pancreatic beta cells, where it has been shown to be fundamental for the initial phase of glucose-induced insulin secretion. To gain mechanistic insight into beta cell autonomous function of PS1, we have examined various beta cell models and found that PS1 controls glycolytic flux of pancreatic beta cells by regulating sub-mitochondrial Ca2+ homeostasis. Transient knock down of PS1 yielded a glycolytic bottleneck at the step catalyzed by glyceraldehyde-3-phosphate dehydrogenase, resulting in defective glucose responsiveness. Moreover, we show that PS1 is needed for the preservation of beta cell identity, likely due to its role in glycolysis. Finally, we show that mouse islets from an in vivo model of AD mimic the defective glucose responsiveness seen in beta cells with transient PS1 knock down, while the identity loss and whole-body glucose homeostasis are not severely impacted, suggesting an adaptive response. Thus, the current work highlights beta cell autonomous role of PS1 and adds a layer of complexity in its impact on whole body metabolism.}, author = {Koshenov, Zhanat and Postic, Sandra and Schoiswohl, Gabriela and Van Amsterdam, Savina and Hois-Zelinka, Victoria and Oflaz, Furkan E. and Rost, Rene and Tiapko, Oleksandra and Gottschalk, Benjamin and Hirtl, Martin and Bachkoenig, Olaf G. and Koshenova, Aigerim and Erdogan, Yusuf C. and Sagintayev, Adlet and Krnjic, Anita and Pfabe, Johannes U. and Sarikas, Srdjan and Hochreiter, Bernhard and Gindlhuber, Juergen and Schittmayer, Matthias and Tadic, Jelena and Ehall, Barbara and Madeo, Frank and Madl, Tobias and Malli, Roland and Birner-Gruenberger, Ruth and Pieber, Thomas and Eisenberg, Tobias and Slak Rupnik, Marjan and Graier, Wolfgang F.}, issn = {2399-3642}, journal = {Communications Biology}, publisher = {Springer Nature}, title = {{Presenilin-1 controls glycolysis and identity of pancreatic beta cells}}, doi = {10.1038/s42003-026-10581-6}, volume = {9}, year = {2026}, } @article{23171, abstract = {Crawling motility is a hallmark of eukaryotic cells and requires a dynamic actin cytoskeleton, regulated adhesion and spatially organized signalling pathways1,2. Asgard archaea, which are considered the closest known prokaryotic relatives of eukaryotes, potentially encode these functions within their large set of ‘eukaryotic signature proteins’3,4,5,6. The few cultivated members show a complex cell morphology, consisting of a central cell body from which several protrusions extend, filled with an actin-based cytoskeleton7,8. Here, live-cell microscopy of two organisms of the Lokiarchaea and Hodarchaea lineages7,9 showed that they dynamically and greatly change their cell shape on a minute time scale and grow and retract their extensive protrusions with a speed of 1.5–4.8 µm min−1, respectively. After adhering to a glass surface, cells use their protrusions to undergo active crawling motion. In the presence of selected actin inhibitors, however, the observed dynamics were arrested, suggesting a central role of actin in these processes. The observed cellular plasticity and motility are unique features among prokaryotes and might have been crucial for the emergence of the first eukaryotic cells that are thought to have formed through the association of a member of the Asgard archaea and an α-proteobacterium, the ancestor of mitochondria.}, author = {Radler, Philipp and Viehboeck, Tobias and Luo, Zhen-Hao and Maslać, Nevena and Schmidt, Katharina and Hauschild, Robert and Nobu, Masaru K. and Bulgheresi, Silvia and Stradal, Theresia E. B. and Rottner, Klemens and Imachi, Hiroyuki and Sixt, Michael K and Schleper, Christa}, issn = {1476-4687}, journal = {Nature}, publisher = {Springer Nature}, title = {{Dynamic protrusions mediate crawling motility in Asgard archaea}}, doi = {10.1038/s41586-026-11063-9}, year = {2026}, } @article{20859, abstract = {Effective immune responses rely on the efficient migration of leukocytes. Yet, how temperature regulates migration dynamics at the single-cell level has remained poorly understood. Using zebrafish embryos and mouse tissue explants, we found that temperature positively regulates leukocyte migration speed, exploration, and arrival frequencies to wounds and lymph vessels. Complementary 2D and 3D cultures revealed that this thermokinetic control of cell migration is conserved across immune cell types, independently of the 3D tissue environment. By applying precise (sub-)cellular temperature modulation, we identified a rapid and reversible thermo-response that depends on myosin II activity. Small physiological increases in temperature (1°C –2°C), as present during fever-like conditions, profoundly increased immune responses by accelerating arrival times at lymphatic vessels and tissue wounds. These findings identify myosin-II-dependent actomyosin contractility as a critical mechanical structure regulating single-cell thermo-adaptability, with physiological implications for tuning the speed of immune responses in vivo.}, author = {Company-Garrido, Iván and Zurita Carpio, Alberto and Colomer-Rosell, Mariona and Ciraulo, Bernard and Molkenbur, Ronja and Lanzerstorfer, Peter and Pezzano, Fabio and Agazzi, Costanza and Hauschild, Robert and Jain, Saumey and Jacques, Jeroen M. and Venturini, Valeria and Knapp, Christian and Xie, Yufei and Merrin, Jack and Weghuber, Julian and Schaaf, Marcel and Quidant, Romain and Kiermaier, Eva and Ortega Arroyo, Jaime and Ruprecht, Verena and Wieser, Stefan}, issn = {1878-1551}, journal = {Developmental Cell}, keywords = {thermobiology, cell migration, thermo-adaptability of immune cells}, number = {2}, pages = {356--371.e12}, publisher = {Cell Press}, title = {{Myosin II regulates cellular thermo-adaptability and the efficiency of immune responses}}, doi = {10.1016/j.devcel.2025.10.006}, volume = {61}, year = {2026}, } @article{21746, abstract = {As vertebrates transitioned from water to land, locomotion shifted from undulatory swimming to limb-based movement. How spinal circuits and their cell types evolved to support this transition remains unclear. We leverage frog metamorphosis, which recapitulates this transition within a single organism, to define how spinal circuits generate aquatic versus terrestrial motor patterns. At swim stages, spinal architecture is uniform, with a transcriptionally and anatomically homogeneous motor and interneurons. As limbs develop and their movement complexifies, spinal circuits expand in neuron number and subtype diversity. This expansion is most pronounced for V1 inhibitory neurons, which increase ∼70-fold and diversify into transcriptionally distinct subtypes. Disrupting transcription factors defining emerging motor and V1 populations reveals molecular segregation between swim and limb circuits, highlighting the role of subtype diversity in motor coordination. A multifold increase in inhibitory neuron diversity thus underlies the tail-to-limb locomotor transition, providing a framework for spinal circuit adaptation during vertebrate evolution.}, author = {Vijatovic, David and Toma, Florina Alexandra and Ignatyev, Y and Harrington, Zoe P and Sommer, Christoph M and Hauschild, Robert and Smits, Matthijs Geert and Dalla Vecchia, Marco and Trevisan, Alexandra J. and Chapman, Phillip and Julseth, Mara and Brenner-Morton, Susan and Gabitto, Mariano I. and Dasen, Jeremy S. and Bikoff, Jay B. and Sweeney, Lora Beatrice Jaeger}, issn = {2211-1247}, journal = {Cell Reports}, number = {4}, publisher = {Cell Press}, title = {{Multifold increase in spinal inhibitory cell types with emergence of limb movement}}, doi = {10.1016/j.celrep.2026.117227}, volume = {45}, year = {2026}, } @inbook{20870, abstract = {RNA sequencing (RNA-seq) methodologies have evolved rapidly, offering powerful tools to study gene expression, transcriptome dynamics, and molecular mechanisms in various biological contexts. However, the complexity of these approaches poses challenges in data interpretation, sensitivity, and applicability. This chapter provides a comprehensive overview of RNA-seq methodologies, highlighting their advantages, limitations, and applications, particularly in cardiovascular research. Bulk RNA sequencing enables high-throughput gene expression profiling but lacks the resolution to capture cellular heterogeneity and spatial context. Direct RNA sequencing preserves native RNA modifications, offering insights into post-transcriptional regulation, though it remains technically challenging. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) bridge these gaps by resolving transcriptomic complexity at the cellular level and within tissue architecture, providing crucial insights into disease mechanisms such as atherosclerosis. By summarizing the strengths and limitations of these methodologies, this chapter aims to guide researchers in selecting the most suitable transcriptomic approach for their studies, ultimately advancing precision medicine and biomarker discovery in cardiovascular disease.}, author = {Stopa, Victoria and Sopić, Miron and Li, Guanliang and Sluimer, Judith and Basílio, José and van der Laan, Sander W. and Kreil, David P. and Devaux, Yvan and Hochreiter, Bernhard}, booktitle = {Transcriptomics in Atherosclerosis}, editor = {Devaux, Yvan and Sopic, Miron}, isbn = {9780443330643}, pages = {131--172}, publisher = {Elsevier}, title = {{Essentials of transcriptomic methods: Navigating through RNA sequencing and beyond}}, doi = {10.1016/b978-0-443-33064-3.00016-5}, year = {2025}, } @misc{19294, abstract = {Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of non-functional “promoter leakiness”, merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the non-canonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g. control of costly-to-induce multi-drug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multi-drug resistance is crucial for effective public health measures.}, author = {Jain, Kirti and Hauschild, Robert and Bochkareva, Olga and Römhild, Roderich and Tkačik, Gašper and Guet, Calin C}, publisher = {Institute of Science and Technology Austria}, title = {{Data for "Pulsatile basal gene expression as a fitness determinant in bacteria"}}, doi = {10.15479/AT:ISTA:19294}, year = {2025}, } @article{19626, abstract = {Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of nonfunctional “promoter leakiness,” merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the noncanonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g., control of costly-to-induce multidrug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multidrug resistance is crucial for effective public health measures.}, author = {Jain, Kirti and Hauschild, Robert and Bochkareva, Olga and Römhild, Roderich and Tkačik, Gašper and Guet, Calin C}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {15}, publisher = {National Academy of Sciences}, title = {{Pulsatile basal gene expression as a fitness determinant in bacteria}}, doi = {10.1073/pnas.2413709122}, volume = {122}, year = {2025}, } @article{19663, abstract = {The centrosome is a microtubule orchestrator, nucleating and anchoring microtubules that grow radially and exert forces on cargos. At the same time, mechanical stresses from the microenvironment and cellular shape changes compress and bend microtubules. Yet, centrosomes are membraneless organelles, raising the question of how centrosomes withstand mechanical forces. Here, we discover that centrosomes can deform and even fracture. We reveal that centrosomes experience deformations during navigational pathfinding within motile cells. Coherence of the centrosome is maintained by Dyrk3 and cNAP1, preventing fracturing by forces. While cells can compensate for the depletion of centriolar-based centrosomes, the fracturing of centrosomes impedes cellular function by generating coexisting microtubule organizing centers that compete during path navigation and thereby cause cellular entanglement in the microenvironment. Our findings show that cells actively maintain the integrity of the centrosome to withstand mechanical forces. These results suggest that centrosome stability preservation is fundamental, given that almost all cells in multicellular organisms experience forces.}, author = {Schmitt, Madeleine T. and Kroll, Janina and Ruiz-Fernandez, Mauricio J.A. and Hauschild, Robert and Ghosh, Shaunak and Kameritsch, Petra and Merrin, Jack and Schmid, Johanna and Stefanowski, Kasia and Thomae, Andreas W. and Cheng, Jingyuan and Öztan, Gamze Naz and Konopka, Peter and Ortega, Germán Camargo and Penz, Thomas and Bach, Luisa and Baumjohann, Dirk and Bock, Christoph and Straub, Tobias and Meissner, Felix and Kiermaier, Eva and Renkawitz, Jörg}, issn = {2375-2548}, journal = {Science Advances}, number = {17}, publisher = {AAAS}, title = {{Protecting centrosomes from fracturing enables efficient cell navigation}}, doi = {10.1126/sciadv.adx4047}, volume = {11}, year = {2025}, } @article{20082, abstract = {Efficient immune responses rely on the capacity of leukocytes to traverse diverse and complex tissues. To meet such changing environmental conditions, leukocytes usually adopt an ameboid configuration, using their forward-positioned nucleus as a probe to identify and follow the path of least resistance among pre-existing pores. We show that, in dense environments where even the largest pores preclude free passage, leukocytes position their nucleus behind the centrosome and organelles. The local compression imposed on the cell body by its surroundings triggers assembly of a central F-actin pool, located between cell front and nucleus. Central actin pushes outward to transiently dilate a path for organelles and nucleus. Pools of central and front actin are tightly coupled and experimental depletion of the central pool enhances actin accumulation and protrusion formation at the cell front. Although this shifted balance speeds up cells in permissive environments, migration in restrictive environments is impaired, as the unleashed leading edge dissociates from the trapped cell body. Our findings establish an actin regulatory loop that balances path dilation with advancement of the leading edge to maintain cellular coherence.}, author = {Dos Reis Rodrigues, Patricia and Avellaneda Sarrió, Mario and Canigova, Nikola and Gärtner, Florian R and Vaahtomeri, Kari and Riedl, Michael and De Vries, Ingrid and Merrin, Jack and Hauschild, Robert and Fukui, Yoshinori and Juanes Garcia, Alba and Sixt, Michael K}, issn = {1529-2916}, journal = {Nature Immunology}, pages = {1258–1266}, publisher = {Springer Nature}, title = {{Migrating immune cells globally coordinate protrusive forces}}, doi = {10.1038/s41590-025-02211-w}, volume = {26}, year = {2025}, } @article{17468, abstract = {Oxygen redox chemistry is central to life1 and many human-made technologies, such as in energy storage2,3,4. The large energy gain from oxygen redox reactions is often connected with the occurrence of harmful reactive oxygen species3,5,6. Key species are superoxide and the highly reactive singlet oxygen3,4,5,6,7, which may evolve from superoxide. However, the factors determining the formation of singlet oxygen, rather than the relatively unreactive triplet oxygen, are unknown. Here we report that the release of triplet or singlet oxygen is governed by individual Marcus normal and inverted region behaviour. We found that as the driving force for the reaction increases, the initially dominant evolution of triplet oxygen slows down, and singlet oxygen evolution becomes predominant with higher maximum kinetics. This behaviour also applies to the widely observed superoxide disproportionation, in which one superoxide is oxidized by another, in both non-aqueous and aqueous systems, with Lewis and Brønsted acidity controlling the driving forces. Singlet oxygen yields governed by these conditions are relevant, for example, in batteries or cellular organelles in which superoxide forms. Our findings suggest ways to understand and control spin states and kinetics in oxygen redox chemistry, with implications for fields, including life sciences, pure chemistry and energy storage.}, author = {Mondal, Soumyadip and Nguyen, Huyen T.K. and Hauschild, Robert and Freunberger, Stefan Alexander}, issn = {1476-4687}, journal = {Nature}, number = {8085}, pages = {601–605}, publisher = {Springer Nature}, title = {{Marcus kinetics control singlet and triplet oxygen evolving from superoxide}}, doi = {10.1038/s41586-025-09587-7}, volume = {646}, year = {2025}, } @article{19704, abstract = {The information-processing capability of the brain’s cellular network depends on the physical wiring pattern between neurons and their molecular and functional characteristics. Mapping neurons and resolving their individual synaptic connections can be achieved by volumetric imaging at nanoscale resolution1,2 with dense cellular labelling. Light microscopy is uniquely positioned to visualize specific molecules, but dense, synapse-level circuit reconstruction by light microscopy has been out of reach, owing to limitations in resolution, contrast and volumetric imaging capability. Here we describe light-microscopy-based connectomics (LICONN). We integrated specifically engineered hydrogel embedding and expansion with comprehensive deep-learning-based segmentation and analysis of connectivity, thereby directly incorporating molecular information into synapse-level reconstructions of brain tissue. LICONN will allow synapse-level phenotyping of brain tissue in biological experiments in a readily adoptable manner.}, author = {Tavakoli, Mojtaba and Lyudchik, Julia and Januszewski, Michał and Vistunou, Vitali and Agudelo Duenas, Nathalie and Vorlaufer, Jakob and Sommer, Christoph M and Kreuzinger, Caroline and Oliveira, Bárbara and Cenameri, Alban and Novarino, Gaia and Jain, Viren and Danzl, Johann G}, issn = {1476-4687}, journal = {Nature}, pages = {398--410}, publisher = {Springer Nature}, title = {{Light-microscopy-based connectomic reconstruction of mammalian brain tissue}}, doi = {10.1038/s41586-025-08985-1}, volume = {642}, year = {2025}, } @article{19404, abstract = {Cell migration is a fundamental process during embryonic development. Most studies in vivo have focused on the migration of cells using the extracellular matrix (ECM) as their substrate for migration. In contrast, much less is known about how cells migrate on other cells, as found in early embryos when the ECM has not yet formed. Here, we show that lateral mesendoderm (LME) cells in the early zebrafish gastrula use the ectoderm as their substrate for migration. We show that the lateral ectoderm is permissive for the animal-pole-directed migration of LME cells, while the ectoderm at the animal pole halts it. These differences in permissiveness depend on the lateral ectoderm being more cohesive than the animal ectoderm, a property controlled by bone morphogenetic protein (BMP) signaling within the ectoderm. Collectively, these findings identify ectoderm tissue cohesion as one critical factor in regulating LME migration during zebrafish gastrulation.}, author = {Tavano, Ste and Brückner, David and Tasciyan, Saren and Tong, Xin and Kardos, Roland and Schauer, Alexandra and Hauschild, Robert and Heisenberg, Carl-Philipp J}, issn = {2211-1247}, journal = {Cell Reports}, number = {3}, publisher = {Cell Press}, title = {{BMP-dependent patterning of ectoderm tissue material properties modulates lateral mesendoderm cell migration during early zebrafish gastrulation}}, doi = {10.1016/j.celrep.2025.115387}, volume = {44}, year = {2025}, } @unpublished{19520, abstract = {Vertebrates exhibit a wide range of motor behaviors, ranging from swimming to complex limb-based movements. Here we take advantage of frog metamorphosis, which captures a swim-to-limb-based movement transformation during the development of a single organism, to explore changes in the underlying spinal circuits. We find that the tadpole spinal cord contains small and largely homogeneous populations of motor neurons (MNs) and V1 interneurons (V1s) at early escape swimming stages. These neuronal populations only modestly increase in number and subtype heterogeneity with the emergence of free swimming. In contrast, during frog metamorphosis and the emergence of limb movement, there is a dramatic expansion of MN and V1 interneuron number and transcriptional heterogeneity, culminating in cohorts of neurons that exhibit striking molecular similarity to mammalian motor circuits. CRISPR/Cas9-mediated gene disruption of the limb MN and V1 determinants FoxP1 and Engrailed-1, respectively, results in severe but selective deficits in tail and limb function. Our work thus demonstrates that neural diversity scales exponentially with increasing behavioral complexity and illustrates striking evolutionary conservation in the molecular organization and function of motor circuits across species.}, author = {Vijatovic, David and Toma, Florina Alexandra and Harrington, Zoe P and Sommer, Christoph M and Hauschild, Robert and Trevisan, Alexandra J. and Chapman, Phillip and Julseth, Mara and Brenner-Morton, Susan and Gabitto, Mariano I. and Dasen, Jeremy S. and Bikoff, Jay B. and Sweeney, Lora Beatrice Jaeger}, booktitle = {bioRxiv}, title = {{Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis}}, doi = {10.1101/2024.09.20.614050}, year = {2024}, } @article{15048, abstract = {Embryogenesis results from the coordinated activities of different signaling pathways controlling cell fate specification and morphogenesis. In vertebrate gastrulation, both Nodal and BMP signaling play key roles in germ layer specification and morphogenesis, yet their interplay to coordinate embryo patterning with morphogenesis is still insufficiently understood. Here, we took a reductionist approach using zebrafish embryonic explants to study the coordination of Nodal and BMP signaling for embryo patterning and morphogenesis. We show that Nodal signaling triggers explant elongation by inducing mesendodermal progenitors but also suppressing BMP signaling activity at the site of mesendoderm induction. Consistent with this, ectopic BMP signaling in the mesendoderm blocks cell alignment and oriented mesendoderm intercalations, key processes during explant elongation. Translating these ex vivo observations to the intact embryo showed that, similar to explants, Nodal signaling suppresses the effect of BMP signaling on cell intercalations in the dorsal domain, thus allowing robust embryonic axis elongation. These findings suggest a dual function of Nodal signaling in embryonic axis elongation by both inducing mesendoderm and suppressing BMP effects in the dorsal portion of the mesendoderm.}, author = {Schauer, Alexandra and Pranjic-Ferscha, Kornelija and Hauschild, Robert and Heisenberg, Carl-Philipp J}, issn = {1477-9129}, journal = {Development}, number = {4}, pages = {1--18}, publisher = {Company of Biologists}, title = {{Robust axis elongation by Nodal-dependent restriction of BMP signaling}}, doi = {10.1242/dev.202316}, volume = {151}, year = {2024}, }