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Cristina Cacho-Navas, Carmen López-Pujante, Natalia Reglero-Real, Natalia Colás-Algora, A Cuervo, Jose Javier Conesa, Susana Barroso, Gema de Rivas, Sergio Ciordia, Alberto Paradela, Gianluca D'Agostino, Carlo Manzo, Jorge Feito, Germán Andrés, Francisca Molina-Jiménez, Pedro Majano, Isabel Correas, J M Carazo, Sussan Nourshargh, Meritxell Huch, Jaime Millán
ICAM-1 nanoclusters regulate hepatic epithelial cell polarity by leukocyte adhesion-independent control of apical actomyosin.
Elife, 12 Art. No. RP89261 (2024)
Open Access PubMed Source   

Epithelial intercellular adhesion molecule (ICAM)-1 is apically polarized, interacts with, and guides leukocytes across epithelial barriers. Polarized hepatic epithelia organize their apical membrane domain into bile canaliculi and ducts, which are not accessible to circulating immune cells but that nevertheless confine most of ICAM-1. Here, by analyzing ICAM-1_KO human hepatic cells, liver organoids from ICAM-1_KO mice and rescue-of-function experiments, we show that ICAM-1 regulates epithelial apicobasal polarity in a leukocyte adhesion-independent manner. ICAM-1 signals to an actomyosin network at the base of canalicular microvilli, thereby controlling the dynamics and size of bile canalicular-like structures. We identified the scaffolding protein EBP50/NHERF1/SLC9A3R1, which connects membrane proteins with the underlying actin cytoskeleton, in the proximity interactome of ICAM-1. EBP50 and ICAM-1 form nano-scale domains that overlap in microvilli, from which ICAM-1 regulates EBP50 nano-organization. Indeed, EBP50 expression is required for ICAM-1-mediated control of BC morphogenesis and actomyosin. Our findings indicate that ICAM-1 regulates the dynamics of epithelial apical membrane domains beyond its role as a heterotypic cell-cell adhesion molecule and reveal potential therapeutic strategies for preserving epithelial architecture during inflammatory stress.
@article{Cacho-Navas8708,
author={Cristina Cacho-Navas, Carmen López-Pujante, Natalia Reglero-Real, Natalia Colás-Algora, A Cuervo, Jose Javier Conesa, Susana Barroso, Gema de Rivas, Sergio Ciordia, Alberto Paradela, Gianluca D'Agostino, Carlo Manzo, Jorge Feito, Germán Andrés, Francisca Molina-Jiménez, Pedro Majano, Isabel Correas, J M Carazo, Sussan Nourshargh, Meritxell Huch, Jaime Millán},
title={ICAM-1 nanoclusters regulate hepatic epithelial cell polarity by leukocyte adhesion-independent control of apical actomyosin.},
journal ={eLife},
volume={12},
pages={null--null},
year=2024
}

Hendrik Frentzel, Marco Kraemer, Ylanna Kelner-Burgos, Laura Uelze, Dorina Bodi
Cereulide production capacities and genetic properties of 31 emetic Bacillus cereus group strains.
Int J Food Microbiol, 417 Art. No. doi: 10.1016/j.ijfoodmicro.2024.110694 (2024)
Open Access PubMed Source   

The highly potent toxin cereulide is a frequent cause of foodborne intoxications. This extremely resistant toxin is produced by Bacillus cereus group strains carrying the plasmid encoded cesHPTABCD gene cluster. It is known that the capacities to produce cereulide vary greatly between different strains but the genetic background of these variations is not clear. In this study, cereulide production capacities were associated with genetic characteristics. For this, cereulide levels in cultures of 31 strains were determined after incubation in tryptic soy broth for 24 h at 24 °C, 30 °C and 37 °C. Whole genome sequencing based data were used for an in-depth characterization of gene sequences related to cereulide production. The taxonomy, population structure and phylogenetic relationships of the strains were evaluated based on average nucleotide identity, multi-locus sequence typing (MLST), core genome MLST and single nucleotide polymorphism analyses. Despite a limited strain number, the approach of a genome wide association study (GWAS) was tested to link genetic variation with cereulide quantities. Our study confirms strain-dependent differences in cereulide production. For most strains, these differences were not explainable by sequence variations in the cesHPTABCD gene cluster or the regulatory genes abrB, spo0A, codY and pagRBc. Likewise, the population structure and phylogeny of the tested strains did not comprehensively reflect the cereulide production capacities. GWAS yielded first hints for associated proteins, while their possible effect on cereulide synthesis remains to be further investigated.
@article{Frentzel8707,
author={Hendrik Frentzel, Marco Kraemer, Ylanna Kelner-Burgos, Laura Uelze, Dorina Bodi},
title={Cereulide production capacities and genetic properties of 31 emetic Bacillus cereus group strains.},
journal ={International journal of food microbiology},
volume={417},
pages={null--null},
year=2024
}

Mukesh Kumar, Canan Has, Khanh Lam-Kamath, Sophie Ayciriex, Deepshe Dewett, Mina Bashir, Clara Poupault, Kai Schuhmann, Henrik Thomas, Oskar Knittelfelder, Bharath Kumar Raghuraman, R Ahrends, Jens Rister#, Andrej Shevchenko#
Lipidome Unsaturation Affects the Morphology and Proteome of the Drosophila Eye.
J Proteome Res, 23(4) 1188-1199 (2024)
Open Access PubMed Source Full Text   

Organisms respond to dietary and environmental challenges by altering the molecular composition of their glycerolipids and glycerophospholipids (GPLs), which may favorably adjust the physicochemical properties of lipid membranes. However, how lipidome changes affect the membrane proteome and, eventually, the physiology of specific organs is an open question. We addressed this issue in Drosophila melanogaster, which is not able to synthesize sterols and polyunsaturated fatty acids but can acquire them from food. We developed a series of semisynthetic foods to manipulate the length and unsaturation of fatty acid moieties in GPLs and singled out proteins whose abundance is specifically affected by membrane lipid unsaturation in the Drosophila eye. Unexpectedly, we identified a group of proteins that have muscle-related functions and increased their abundances under unsaturated eye lipidome conditions. In contrast, the abundance of two stress response proteins, Turandot A and Smg5, is decreased by lipid unsaturation. Our findings could guide the genetic dissection of homeostatic mechanisms that maintain visual function when the eye is exposed to environmental and dietary challenges.
@article{Kumar8697,
author={Mukesh Kumar, Canan Has, Khanh Lam-Kamath, Sophie Ayciriex, Deepshe Dewett, Mina Bashir, Clara Poupault, Kai Schuhmann, Henrik Thomas, Oskar Knittelfelder, Bharath Kumar Raghuraman, R Ahrends, Jens Rister, Andrej Shevchenko},
title={Lipidome Unsaturation Affects the Morphology and Proteome of the Drosophila Eye.},
journal ={Journal of proteome research},
volume={23},
issue ={4},
pages={1188--1199},
year=2024
}

Adriano Bolondi✳︎, Benjamin K Law✳︎, Helene Kretzmer, Seher Ipek Gassaloglu, René Buschow, Christina Riemenschneider, Dian Yang, Maria Walther, Jesse V Veenvliet, Alexander Meissner#, Zachary D Smith#, Michelle M Chan#
Reconstructing axial progenitor field dynamics in mouse stem cell-derived embryoids.
Dev Cell, Art. No. doi: 10.1016/j.devcel.2024.03.024 (2024)
Open Access PubMed Source   

Embryogenesis requires substantial coordination to translate genetic programs to the collective behavior of differentiating cells, but understanding how cellular decisions control tissue morphology remains conceptually and technically challenging. Here, we combine continuous Cas9-based molecular recording with a mouse embryonic stem cell-based model of the embryonic trunk to build single-cell phylogenies that describe the behavior of transient, multipotent neuro-mesodermal progenitors (NMPs) as they commit into neural and somitic cell types. We find that NMPs show subtle transcriptional signatures related to their recent differentiation and contribute to downstream lineages through a surprisingly broad distribution of individual fate outcomes. Although decision-making can be heavily influenced by environmental cues to induce morphological phenotypes, axial progenitors intrinsically mature over developmental time to favor the neural lineage. Using these data, we present an experimental and analytical framework for exploring the non-homeostatic dynamics of transient progenitor populations as they shape complex tissues during critical developmental windows.
@article{Bolondi8700,
author={Adriano Bolondi, Benjamin K Law, Helene Kretzmer, Seher Ipek Gassaloglu, René Buschow, Christina Riemenschneider, Dian Yang, Maria Walther, Jesse V Veenvliet, Alexander Meissner, Zachary D Smith, Michelle M Chan},
title={Reconstructing axial progenitor field dynamics in mouse stem cell-derived embryoids.},
journal ={Developmental cell},
volume={},
pages={1--1},
year=2024
}

Oliver Kutz, Stephan Drukewitz, Alexander Krüger, Daniela Aust, Doreen William, Sandra Oster, Evelin Schröck, Gustavo Baretton, Theresa Link, Pauline Wimberger, Jan Dominik Kuhlmann
Exploring evolutionary trajectories in ovarian cancer patients by longitudinal analysis of ctDNA.
Clin Chem Lab Med, Art. No. doi: 10.1515/cclm-2023-1266 (2024)
PubMed Source   

We analysed whether temporal heterogeneity of ctDNA encodes evolutionary patterns in ovarian cancer.
@article{Kutz8701,
author={Oliver Kutz, Stephan Drukewitz, Alexander Krüger, Daniela Aust, Doreen William, Sandra Oster, Evelin Schröck, Gustavo Baretton, Theresa Link, Pauline Wimberger, Jan Dominik Kuhlmann},
title={Exploring evolutionary trajectories in ovarian cancer patients by longitudinal analysis of ctDNA.},
journal ={Clinical chemistry and laboratory medicine},
volume={},
pages={1--1},
year=2024
}

Neha Pincha Shroff✳︎, Pengfei Xu✳︎, Sangwoo Kim, Elijah R Shelton, Ben J Gross, Yucen Liu, Carlos O Gomez, Qianlin Ye, Tingsheng Yu Drennon, Jimmy K Hu, Jeremy B A Green, Otger Campàs#, Ophir D. Klein#
Proliferation-driven mechanical compression induces signalling centre formation during mammalian organ development.
Nat Cell Biol, Art. No. doi: 10.1038/s41556-024-01380-4 (2024)
PubMed Source   

Localized sources of morphogens, called signalling centres, play a fundamental role in coordinating tissue growth and cell fate specification during organogenesis. However, how these signalling centres are established in tissues during embryonic development is still unclear. Here we show that the main signalling centre orchestrating development of rodent incisors, the enamel knot (EK), is specified by a cell proliferation-driven buildup in compressive stresses (mechanical pressure) in the tissue. Direct mechanical measurements indicate that the stresses generated by cell proliferation are resisted by the surrounding tissue, creating a circular pattern of mechanical anisotropy with a region of high compressive stress at its centre that becomes the EK. Pharmacological inhibition of proliferation reduces stresses and suppresses EK formation, and application of external pressure in proliferation-inhibited conditions rescues the formation of the EK. Mechanical information is relayed intracellularly through YAP protein localization, which is cytoplasmic in the region of compressive stress that establishes the EK and nuclear in the stretched anisotropic cells that resist the pressure buildup around the EK. Together, our data identify a new role for proliferation-driven mechanical compression in the specification of a model signalling centre during mammalian organ development.
@article{Shroff8702,
author={Neha Pincha Shroff, Pengfei Xu, Sangwoo Kim, Elijah R Shelton, Ben J Gross, Yucen Liu, Carlos O Gomez, Qianlin Ye, Tingsheng Yu Drennon, Jimmy K Hu, Jeremy B A Green, Otger Campàs, Ophir D. Klein},
title={Proliferation-driven mechanical compression induces signalling centre formation during mammalian organ development.},
journal ={Nature cell biology},
volume={},
pages={1--1},
year=2024
}

Otger Campàs#, Ivar Noordstra, Alpha S Yap#
Adherens junctions as molecular regulators of emergent tissue mechanics.
Nat Rev Mol Cell Biol, 25(4) 252-269 (2024)
PubMed Source   

Tissue and organ development during embryogenesis relies on the collective and coordinated action of many cells. Recent studies have revealed that tissue material properties, including transitions between fluid and solid tissue states, are controlled in space and time to shape embryonic structures and regulate cell behaviours. Although the collective cellular flows that sculpt tissues are guided by tissue-level physical changes, these ultimately emerge from cellular-level and subcellular-level molecular mechanisms. Adherens junctions are key subcellular structures, built from clusters of classical cadherin receptors. They mediate physical interactions between cells and connect biochemical signalling to the physical characteristics of cell contacts, hence playing a fundamental role in tissue morphogenesis. In this Review, we take advantage of the results of recent, quantitative measurements of tissue mechanics to relate the molecular and cellular characteristics of adherens junctions, including adhesion strength, tension and dynamics, to the emergent physical state of embryonic tissues. We focus on systems in which cell-cell interactions are the primary contributor to morphogenesis, without significant contribution from cell-matrix interactions. We suggest that emergent tissue mechanics is an important direction for future research, bridging cell biology, developmental biology and mechanobiology to provide a holistic understanding of morphogenesis in health and disease.
@article{Campàs8649,
author={Otger Campàs, Ivar Noordstra, Alpha S Yap},
title={Adherens junctions as molecular regulators of emergent tissue mechanics.},
journal ={Nature reviews. Molecular cell biology},
volume={25},
issue ={4},
pages={252--269},
year=2024
}

Ferenc Molnár, Szabolcs Horvát, Ana R. Ribeiro Gomes, Jorge Martinez Armas, Botond Molnár, Robert F Hevner, Kenneth Knoblauch, Henry Kennedy, Zoltan Toroczkai
Predictability of cortico-cortical connections in the mammalian brain.
Network Neuroscience, 8(1) 138-157 (2024)
Open Access Source   

Despite a five order of magnitude range in size, the brains of mammals share many anatomical and functional characteristics that translate into cortical network commonalities. Here we develop a machine learning framework to quantify the degree of predictability of the weighted interareal cortical matrix. Partial network connectivity data were obtained with retrograde tract-tracing experiments generated with a consistent methodology, supplemented by projection length measurements in a nonhuman primate (macaque) and a rodent (mouse). We show that there is a significant level of predictability embedded in the interareal cortical networks of both species. At the binary level, links are predictable with an area under the ROC curve of at least 0.8 for the macaque. Weighted medium and strong links are predictable with an 85%-90% accuracy (mouse) and 70%-80% (macaque), whereas weak links are not predictable in either species. These observations reinforce earlier observations that the formation and evolution of the cortical network at the mesoscale is, to a large extent, rule based. Using the methodology presented here, we performed imputations on all area pairs, generating samples for the complete interareal network in both species. These are necessary for comparative studies of the connectome with minimal bias, both within and across species. Revealed by tract-tracing datasets, communication between the functional areas of the cortex operates via a complex, dense, and weighted network of physical connections with little apparent regularity. Although there are studies showing the existence of nonrandom topological features, their extent has not been clear. Employing a machine learning-based approach, which efficiently extracts structural models from such datasets, here we show that there is a significant amount of regularity embedded in the mammalian connectome. This regularity allows predicting interareal connections and their weights with good accuracy and can be used to infer properties of experimentally untested connections. The structural models are well learned even with small training sets, without overfitting, suggesting the existence of a low-dimensional, universal mechanism for mesoscale cortical network formation and evolution.
@article{Molnár8695,
author={Ferenc Molnár, Szabolcs Horvát, Ana R. Ribeiro Gomes, Jorge Martinez Armas, Botond Molnár, Robert F Hevner, Kenneth Knoblauch, Henry Kennedy, Zoltan Toroczkai},
title={Predictability of cortico-cortical connections in the mammalian brain.},
journal ={Network Neuroscience},
volume={8},
issue ={1},
pages={138--157},
year=2024
}

Martino Ugolini, Maciej A Kerlin, Ksenia Kuznetsova, Haruka Oda, Hiroshi Kimura, Nadine Vastenhouw
Transcription bodies regulate gene expression by sequestering CDK9.
Nat Cell Biol, 26(4) 604-612 (2024)
Open Access PubMed Source   

The localization of transcriptional activity in specialized transcription bodies is a hallmark of gene expression in eukaryotic cells. It remains unclear, however, if and how transcription bodies affect gene expression. Here we disrupted the formation of two prominent endogenous transcription bodies that mark the onset of zygotic transcription in zebrafish embryos and analysed the effect on gene expression using enriched SLAM-seq and live-cell imaging. We find that the disruption of transcription bodies results in the misregulation of hundreds of genes. Here we focus on genes that are upregulated. These genes have accessible chromatin and are poised to be transcribed in the presence of the two transcription bodies, but they do not go into elongation. Live-cell imaging shows that disruption of the two large transcription bodies enables these poised genes to be transcribed in ectopic transcription bodies, suggesting that the large transcription bodies sequester a pause release factor. Supporting this hypothesis, we find that CDK9-the kinase that releases paused polymerase II-is highly enriched in the two large transcription bodies. Overexpression of CDK9 in wild-type embryos results in the formation of ectopic transcription bodies and thus phenocopies the removal of the two large transcription bodies. Taken together, our results show that transcription bodies regulate transcription by sequestering machinery, thereby preventing genes elsewhere in the nucleus from being transcribed.
@article{Ugolini8709,
author={Martino Ugolini, Maciej A Kerlin, Ksenia Kuznetsova, Haruka Oda, Hiroshi Kimura, Nadine Vastenhouw},
title={Transcription bodies regulate gene expression by sequestering CDK9.},
journal ={Nature cell biology},
volume={26},
issue ={4},
pages={604--612},
year=2024
}

Bethan Clark, Aaron Hickey, Aleksandra Marconi, Bettina Fischer, Joel Elkin, Rita Mateus, M Emília Santos
Developmental plasticity and variability in the formation of egg-spots, a pigmentation ornament in the cichlid Astatotilapia calliptera.
Evol Dev, Art. No. doi: 10.1111/ede.12475 (2024)
Open Access PubMed Source   

Vertebrate pigmentation patterns are highly diverse, yet we have a limited understanding of how evolutionary changes to genetic, cellular, and developmental mechanisms generate variation. To address this, we examine the formation of a sexually-selected male ornament exhibiting inter- and intraspecific variation, the egg-spot pattern, consisting of circular yellow-orange markings on the male anal fins of haplochromine cichlid fishes. We focus on Astatotilapia calliptera, the ancestor-type species of the Malawi cichlid adaptive radiation of over 850 species. We identify a key role for iridophores in initializing egg-spot aggregations composed of iridophore-xanthophore associations. Despite adult sexual dimorphism, aggregations initially form in both males and females, with development only diverging between the sexes at later stages. Unexpectedly, we found that the timing of egg-spot initialization is plastic. The earlier individuals are socially isolated, the earlier the aggregations form, with iridophores being the cell type that responds to changes to the social environment. Furthermore, we observe apparent competitive interactions between adjacent egg-spot aggregations, which strongly suggests that egg-spot patterning results mostly from cell-autonomous cellular interactions. Together, these results demonstrate that A. calliptera egg-spot development is an exciting model for investigating pigment pattern formation at the cellular level in a system with developmental plasticity, sexual dimorphism, and intraspecific variation. As A. calliptera represents the ancestral bauplan for egg-spots, these findings provide a baseline for informed comparisons across the incredibly diverse Malawi cichlid radiation.
@article{Clark8705,
author={Bethan Clark, Aaron Hickey, Aleksandra Marconi, Bettina Fischer, Joel Elkin, Rita Mateus, M Emília Santos},
title={Developmental plasticity and variability in the formation of egg-spots, a pigmentation ornament in the cichlid Astatotilapia calliptera.},
journal ={Evolution & development},
volume={},
pages={1--1},
year=2024
}
✳︎ joint first authors, # joint corresponding authors
--%>