@article{12217,
abstract = {The development dynamics and self-organization of glandular branched epithelia is of utmost importance for our understanding of diverse processes ranging from normal tissue growth to the growth of cancerous tissues. Using single primary murine pancreatic ductal adenocarcinoma (PDAC) cells embedded in a collagen matrix and adapted media supplementation, we generate organoids that self-organize into highly branched structures displaying a seamless lumen connecting terminal end buds, replicating in vivo PDAC architecture. We identify distinct morphogenesis phases, each characterized by a unique pattern of cell invasion, matrix deformation, protein expression, and respective molecular dependencies. We propose a minimal theoretical model of a branching and proliferating tissue, capturing the dynamics of the first phases. Observing the interaction of morphogenesis, mechanical environment and gene expression in vitro sets a benchmark for the understanding of self-organization processes governing complex organoid structure formation processes and branching morphogenesis.},
author = {Randriamanantsoa, S. and Papargyriou, A. and Maurer, H. C. and Peschke, K. and Schuster, M. and Zecchin, G. and Steiger, K. and Öllinger, R. and Saur, D. and Scheel, C. and Rad, R. and Hannezo, Edouard B and Reichert, M. and Bausch, A. R.},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
publisher = {Springer Nature},
title = {{Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids}},
doi = {10.1038/s41467-022-32806-y},
volume = {13},
year = {2022},
}
@article{12224,
abstract = {Muskelin (Mkln1) is implicated in neuronal function, regulating plasma membrane receptor trafficking. However, its influence on intrinsic brain activity and corresponding behavioral processes remains unclear. Here we show that murine Mkln1 knockout causes non-habituating locomotor activity, increased exploratory drive, and decreased locomotor response to amphetamine. Muskelin deficiency impairs social novelty detection while promoting the retention of spatial reference memory and fear extinction recall. This is strongly mirrored in either weaker or stronger resting-state functional connectivity between critical circuits mediating locomotor exploration and cognition. We show that Mkln1 deletion alters dendrite branching and spine structure, coinciding with enhanced AMPAR-mediated synaptic transmission but selective impairment in synaptic potentiation maintenance. We identify muskelin at excitatory synapses and highlight its role in regulating dendritic spine actin stability. Our findings point to aberrant spine actin modulation and changes in glutamatergic synaptic function as critical mechanisms that contribute to the neurobehavioral phenotype arising from Mkln1 ablation.},
author = {Muhia, Mary W and YuanXiang, PingAn and Sedlacik, Jan and Schwarz, Jürgen R. and Heisler, Frank F. and Gromova, Kira V. and Thies, Edda and Breiden, Petra and Pechmann, Yvonne and Kreutz, Michael R. and Kneussel, Matthias},
issn = {2399-3642},
journal = {Communications Biology},
keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology, Medicine (miscellaneous)},
publisher = {Springer Nature},
title = {{Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes}},
doi = {10.1038/s42003-022-03446-1},
volume = {5},
year = {2022},
}
@article{12231,
abstract = {Ventral tail bending, which is transient but pronounced, is found in many chordate embryos and constitutes an interesting model of how tissue interactions control embryo shape. Here, we identify one key upstream regulator of ventral tail bending in embryos of the ascidian Ciona. We show that during the early tailbud stages, ventral epidermal cells exhibit a boat-shaped morphology (boat cell) with a narrow apical surface where phosphorylated myosin light chain (pMLC) accumulates. We further show that interfering with the function of the BMP ligand Admp led to pMLC localizing to the basal instead of the apical side of ventral epidermal cells and a reduced number of boat cells. Finally, we show that cutting ventral epidermal midline cells at their apex using an ultraviolet laser relaxed ventral tail bending. Based on these results, we propose a previously unreported function for Admp in localizing pMLC to the apical side of ventral epidermal cells, which causes the tail to bend ventrally by resisting antero-posterior notochord extension at the ventral side of the tail.},
author = {Kogure, Yuki S. and Muraoka, Hiromochi and Koizumi, Wataru C. and Gelin-alessi, Raphaël and Godard, Benoit G and Oka, Kotaro and Heisenberg, Carl-Philipp J and Hotta, Kohji},
issn = {1477-9129},
journal = {Development},
keywords = {Developmental Biology, Molecular Biology},
number = {21},
publisher = {The Company of Biologists},
title = {{Admp regulates tail bending by controlling ventral epidermal cell polarity via phosphorylated myosin localization in Ciona}},
doi = {10.1242/dev.200215},
volume = {149},
year = {2022},
}
@article{12238,
abstract = {Upon the initiation of collective cell migration, the cells at the free edge are specified as leader cells; however, the mechanism underlying the leader cell specification remains elusive. Here, we show that lamellipodial extension after the release from mechanical confinement causes sustained extracellular signal-regulated kinase (ERK) activation and underlies the leader cell specification. Live-imaging of Madin-Darby canine kidney (MDCK) cells and mouse epidermis through the use of Förster resonance energy transfer (FRET)-based biosensors showed that leader cells exhibit sustained ERK activation in a hepatocyte growth factor (HGF)-dependent manner. Meanwhile, follower cells exhibit oscillatory ERK activation waves in an epidermal growth factor (EGF) signaling-dependent manner. Lamellipodial extension at the free edge increases the cellular sensitivity to HGF. The HGF-dependent ERK activation, in turn, promotes lamellipodial extension, thereby forming a positive feedback loop between cell extension and ERK activation and specifying the cells at the free edge as the leader cells. Our findings show that the integration of physical and biochemical cues underlies the leader cell specification during collective cell migration.},
author = {Hino, Naoya and Matsuda, Kimiya and Jikko, Yuya and Maryu, Gembu and Sakai, Katsuya and Imamura, Ryu and Tsukiji, Shinya and Aoki, Kazuhiro and Terai, Kenta and Hirashima, Tsuyoshi and Trepat, Xavier and Matsuda, Michiyuki},
issn = {1534-5807},
journal = {Developmental Cell},
keywords = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology},
number = {19},
pages = {2290--2304.e7},
publisher = {Elsevier},
title = {{A feedback loop between lamellipodial extension and HGF-ERK signaling specifies leader cells during collective cell migration}},
doi = {10.1016/j.devcel.2022.09.003},
volume = {57},
year = {2022},
}
@article{12239,
abstract = {Biological systems are the sum of their dynamic three-dimensional (3D) parts. Therefore, it is critical to study biological structures in 3D and at high resolution to gain insights into their physiological functions. Electron microscopy of metal replicas of unroofed cells and isolated organelles has been a key technique to visualize intracellular structures at nanometer resolution. However, many of these methods require specialized equipment and personnel to complete them. Here, we present novel accessible methods to analyze biological structures in unroofed cells and biochemically isolated organelles in 3D and at nanometer resolution, focusing on Arabidopsis clathrin-coated vesicles (CCVs). While CCVs are essential trafficking organelles, their detailed structural information is lacking due to their poor preservation when observed via classical electron microscopy protocols experiments. First, we establish a method to visualize CCVs in unroofed cells using scanning transmission electron microscopy tomography, providing sufficient resolution to define the clathrin coat arrangements. Critically, the samples are prepared directly on electron microscopy grids, removing the requirement to use extremely corrosive acids, thereby enabling the use of this method in any electron microscopy lab. Secondly, we demonstrate that this standardized sample preparation allows the direct comparison of isolated CCV samples with those visualized in cells. Finally, to facilitate the high-throughput and robust screening of metal replicated samples, we provide a deep learning analysis method to screen the “pseudo 3D” morphologies of CCVs imaged with 2D modalities. Collectively, our work establishes accessible ways to examine the 3D structure of biological samples and provide novel insights into the structure of plant CCVs.},
author = {Johnson, Alexander J and Kaufmann, Walter and Sommer, Christoph M and Costanzo, Tommaso and Dahhan, Dana A. and Bednarek, Sebastian Y. and Friml, Jiří},
issn = {1674-2052},
journal = {Molecular Plant},
keywords = {Plant Science, Molecular Biology},
number = {10},
pages = {1533--1542},
publisher = {Elsevier},
title = {{Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution}},
doi = {10.1016/j.molp.2022.09.003},
volume = {15},
year = {2022},
}
@article{12245,
abstract = {MicroRNAs (miRs) have an important role in tuning dynamic gene expression. However, the mechanism by which they are quantitatively controlled is unknown. We show that the amount of mature miR-9, a key regulator of neuronal development, increases during zebrafish neurogenesis in a sharp stepwise manner. We characterize the spatiotemporal profile of seven distinct microRNA primary transcripts (pri-mir)-9s that produce the same mature miR-9 and show that they are sequentially expressed during hindbrain neurogenesis. Expression of late-onset pri-mir-9-1 is added on to, rather than replacing, the expression of early onset pri-mir-9-4 and -9-5 in single cells. CRISPR/Cas9 mutation of the late-onset pri-mir-9-1 prevents the developmental increase of mature miR-9, reduces late neuronal differentiation and fails to downregulate Her6 at late stages. Mathematical modelling shows that an adaptive network containing Her6 is insensitive to linear increases in miR-9 but responds to stepwise increases of miR-9. We suggest that a sharp stepwise increase of mature miR-9 is created by sequential and additive temporal activation of distinct loci. This may be a strategy to overcome adaptation and facilitate a transition of Her6 to a new dynamic regime or steady state.},
author = {Soto, Ximena and Burton, Joshua and Manning, Cerys S. and Minchington, Thomas and Lea, Robert and Lee, Jessica and Kursawe, Jochen and Rattray, Magnus and Papalopulu, Nancy},
issn = {1477-9129},
journal = {Development},
keywords = {Developmental Biology, Molecular Biology},
number = {19},
publisher = {The Company of Biologists},
title = {{Sequential and additive expression of miR-9 precursors control timing of neurogenesis}},
doi = {10.1242/dev.200474},
volume = {149},
year = {2022},
}
@article{12261,
abstract = {Dose–response relationships are a general concept for quantitatively describing biological systems across multiple scales, from the molecular to the whole-cell level. A clinically relevant example is the bacterial growth response to antibiotics, which is routinely characterized by dose–response curves. The shape of the dose–response curve varies drastically between antibiotics and plays a key role in treatment, drug interactions, and resistance evolution. However, the mechanisms shaping the dose–response curve remain largely unclear. Here, we show in Escherichia coli that the distinctively shallow dose–response curve of the antibiotic trimethoprim is caused by a negative growth-mediated feedback loop: Trimethoprim slows growth, which in turn weakens the effect of this antibiotic. At the molecular level, this feedback is caused by the upregulation of the drug target dihydrofolate reductase (FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim but follows a universal trend line that depends primarily on the growth rate, irrespective of its cause. Rewiring the feedback loop alters the dose–response curve in a predictable manner, which we corroborate using a mathematical model of cellular resource allocation and growth. Our results indicate that growth-mediated feedback loops may shape drug responses more generally and could be exploited to design evolutionary traps that enable selection against drug resistance.},
author = {Angermayr, Andreas and Pang, Tin Yau and Chevereau, Guillaume and Mitosch, Karin and Lercher, Martin J and Bollenbach, Mark Tobias},
issn = {1744-4292},
journal = {Molecular Systems Biology},
keywords = {Applied Mathematics, Computational Theory and Mathematics, General Agricultural and Biological Sciences, General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, Information Systems},
number = {9},
publisher = {Embo Press},
title = {{Growth‐mediated negative feedback shapes quantitative antibiotic response}},
doi = {10.15252/msb.202110490},
volume = {18},
year = {2022},
}
@article{12262,
abstract = {The AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis that initiates cytoplasmic maturation of the large ribosomal subunit. Drg1 releases the shuttling maturation factor Rlp24 from pre-60S particles shortly after nuclear export, a strict requirement for downstream maturation. The molecular mechanism of release remained elusive. Here, we report a series of cryo-EM structures that captured the extraction of Rlp24 from pre-60S particles by Saccharomyces cerevisiae Drg1. These structures reveal that Arx1 and the eukaryote-specific rRNA expansion segment ES27 form a joint docking platform that positions Drg1 for efficient extraction of Rlp24 from the pre-ribosome. The tips of the Drg1 N domains thereby guide the Rlp24 C terminus into the central pore of the Drg1 hexamer, enabling extraction by a hand-over-hand translocation mechanism. Our results uncover substrate recognition and processing by Drg1 step by step and provide a comprehensive mechanistic picture of the conserved modus operandi of AAA-ATPases.},
author = {Prattes, Michael and Grishkovskaya, Irina and Hodirnau, Victor-Valentin and Hetzmannseder, Christina and Zisser, Gertrude and Sailer, Carolin and Kargas, Vasileios and Loibl, Mathias and Gerhalter, Magdalena and Kofler, Lisa and Warren, Alan J. and Stengel, Florian and Haselbach, David and Bergler, Helmut},
issn = {1545-9985},
journal = {Nature Structural & Molecular Biology},
keywords = {Molecular Biology, Structural Biology},
number = {9},
pages = {942--953},
publisher = {Springer Nature},
title = {{Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1}},
doi = {10.1038/s41594-022-00832-5},
volume = {29},
year = {2022},
}
@article{12275,
abstract = {N-glycans are molecularly diverse sugars borne by over 70% of proteins transiting the secretory pathway and have been implicated in protein folding, stability, and localization. Mutations in genes important for N-glycosylation result in congenital disorders of glycosylation that are often associated with intellectual disability. Here, we show that structurally distinct N-glycans regulate an extracellular protein complex involved in the patterning of somatosensory dendrites in Caenorhabditis elegans. Specifically, aman-2/Golgi alpha-mannosidase II, a conserved key enzyme in the biosynthesis of specific N-glycans, regulates the activity of the Menorin adhesion complex without obviously affecting the protein stability and localization of its components. AMAN-2 functions cell-autonomously to allow for decoration of the neuronal transmembrane receptor DMA-1/LRR-TM with the correct set of high-mannose/hybrid/paucimannose N-glycans. Moreover, distinct types of N-glycans on specific N-glycosylation sites regulate DMA-1/LRR-TM receptor function, which, together with three other extracellular proteins, forms the Menorin adhesion complex. In summary, specific N-glycan structures regulate dendrite patterning by coordinating the activity of an extracellular adhesion complex, suggesting that the molecular diversity of N-glycans can contribute to developmental specificity in the nervous system.},
author = {Rahman, Maisha and Ramirez, Nelson and Diaz‐Balzac, Carlos A and Bülow, Hannes E},
issn = {1469-3178},
journal = {EMBO Reports},
keywords = {Genetics, Molecular Biology, Biochemistry},
number = {7},
publisher = {Embo Press},
title = {{Specific N-glycans regulate an extracellular adhesion complex during somatosensory dendrite patterning}},
doi = {10.15252/embr.202154163},
volume = {23},
year = {2022},
}
@article{12280,
abstract = {In repeated interactions, players can use strategies that respond to the outcome of previous rounds. Much of the existing literature on direct reciprocity assumes that all competing individuals use the same strategy space. Here, we study both learning and evolutionary dynamics of players that differ in the strategy space they explore. We focus on the infinitely repeated donation game and compare three natural strategy spaces: memory-1 strategies, which consider the last moves of both players, reactive strategies, which respond to the last move of the co-player, and unconditional strategies. These three strategy spaces differ in the memory capacity that is needed. We compute the long term average payoff that is achieved in a pairwise learning process. We find that smaller strategy spaces can dominate larger ones. For weak selection, unconditional players dominate both reactive and memory-1 players. For intermediate selection, reactive players dominate memory-1 players. Only for strong selection and low cost-to-benefit ratio, memory-1 players dominate the others. We observe that the supergame between strategy spaces can be a social dilemma: maximum payoff is achieved if both players explore a larger strategy space, but smaller strategy spaces dominate.},
author = {Schmid, Laura and Hilbe, Christian and Chatterjee, Krishnendu and Nowak, Martin},
issn = {1553-7358},
journal = {PLOS Computational Biology},
keywords = {Computational Theory and Mathematics, Cellular and Molecular Neuroscience, Genetics, Molecular Biology, Ecology, Modeling and Simulation, Ecology, Evolution, Behavior and Systematics},
number = {6},
publisher = {Public Library of Science},
title = {{Direct reciprocity between individuals that use different strategy spaces}},
doi = {10.1371/journal.pcbi.1010149},
volume = {18},
year = {2022},
}
@article{12288,
abstract = {To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo.},
author = {Sumser, Anton L and Jösch, Maximilian A and Jonas, Peter M and Ben Simon, Yoav},
issn = {2050-084X},
journal = {eLife},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
publisher = {eLife Sciences Publications},
title = {{Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling}},
doi = {10.7554/elife.79848},
volume = {11},
year = {2022},
}
@article{12670,
abstract = {DNA methylation plays essential homeostatic functions in eukaryotic genomes. In animals, DNA methylation is also developmentally regulated and, in turn, regulates development. In the past two decades, huge research effort has endorsed the understanding that DNA methylation plays a similar role in plant development, especially during sexual reproduction. The power of whole-genome sequencing and cell isolation techniques, as well as bioinformatics tools, have enabled recent studies to reveal dynamic changes in DNA methylation during germline development. Furthermore, the combination of these technological advances with genetics, developmental biology and cell biology tools has revealed functional methylation reprogramming events that control gene and transposon activities in flowering plant germlines. In this review, we discuss the major advances in our knowledge of DNA methylation dynamics during male and female germline development in flowering plants.},
author = {He, Shengbo and Feng, Xiaoqi},
issn = {1744-7909},
journal = {Journal of Integrative Plant Biology},
keywords = {Plant Science, General Biochemistry, Genetics and Molecular Biology, Biochemistry},
number = {12},
pages = {2240--2251},
publisher = {Wiley},
title = {{DNA methylation dynamics during germline development}},
doi = {10.1111/jipb.13422},
volume = {64},
year = {2022},
}
@article{10787,
abstract = {A species distributed across diverse environments may adapt to local conditions. We ask how quickly such a species changes its range in response to changed conditions. Szép et al. (Szép E, Sachdeva H, Barton NH. 2021 Polygenic local adaptation in metapopulations: a stochastic eco-evolutionary model. Evolution75, 1030–1045 (doi:10.1111/evo.14210)) used the infinite island model to find the stationary distribution of allele frequencies and deme sizes. We extend this to find how a metapopulation responds to changes in carrying capacity, selection strength, or migration rate when deme sizes are fixed. We further develop a ‘fixed-state’ approximation. Under this approximation, polymorphism is only possible for a narrow range of habitat proportions when selection is weak compared to drift, but for a much wider range otherwise. When rates of selection or migration relative to drift change in a single deme of the metapopulation, the population takes a time of order m−1 to reach the new equilibrium. However, even with many loci, there can be substantial fluctuations in net adaptation, because at each locus, alleles randomly get lost or fixed. Thus, in a finite metapopulation, variation may gradually be lost by chance, even if it would persist in an infinite metapopulation. When conditions change across the whole metapopulation, there can be rapid change, which is predicted well by the fixed-state approximation. This work helps towards an understanding of how metapopulations extend their range across diverse environments.
This article is part of the theme issue ‘Species’ ranges in the face of changing environments (Part II)’.},
author = {Barton, Nicholas H and Olusanya, Oluwafunmilola O},
issn = {1471-2970},
journal = {Philosophical Transactions of the Royal Society B: Biological Sciences},
keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology},
number = {1848},
publisher = {The Royal Society},
title = {{The response of a metapopulation to a changing environment}},
doi = {10.1098/rstb.2021.0009},
volume = {377},
year = {2022},
}
@article{11160,
abstract = {Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling.},
author = {Villa, Carlo Emanuele and Cheroni, Cristina and Dotter, Christoph and López-Tóbon, Alejandro and Oliveira, Bárbara and Sacco, Roberto and Yahya, Aysan Çerağ and Morandell, Jasmin and Gabriele, Michele and Tavakoli, Mojtaba and Lyudchik, Julia and Sommer, Christoph M and Gabitto, Mariano and Danzl, Johann G and Testa, Giuseppe and Novarino, Gaia},
issn = {2211-1247},
journal = {Cell Reports},
keywords = {General Biochemistry, Genetics and Molecular Biology},
number = {1},
publisher = {Elsevier},
title = {{CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories}},
doi = {10.1016/j.celrep.2022.110615},
volume = {39},
year = {2022},
}
@article{11167,
abstract = {Complex I is one of the major respiratory complexes, conserved from bacteria to mammals. It oxidises NADH, reduces quinone and pumps protons across the membrane, thus playing a central role in the oxidative energy metabolism. In this review we discuss our current state of understanding the structure of complex I from various species of mammals, plants, fungi, and bacteria, as well as of several complex I-related proteins. By comparing the structural evidence from these systems in different redox states and data from mutagenesis and molecular simulations, we formulate the mechanisms of electron transfer and proton pumping and explain how they are conformationally and electrostatically coupled. Finally, we discuss the structural basis of the deactivation phenomenon in mammalian complex I.},
author = {Kampjut, Domen and Sazanov, Leonid A},
issn = {0959-440X},
journal = {Current Opinion in Structural Biology},
keywords = {Molecular Biology, Structural Biology},
publisher = {Elsevier},
title = {{Structure of respiratory complex I – An emerging blueprint for the mechanism}},
doi = {10.1016/j.sbi.2022.102350},
volume = {74},
year = {2022},
}
@article{11351,
abstract = {One hallmark of plant cells is their cell wall. They protect cells against the environment and high turgor and mediate morphogenesis through the dynamics of their mechanical and chemical properties. The walls are a complex polysaccharidic structure. Although their biochemical composition is well known, how the different components organize in the volume of the cell wall and interact with each other is not well understood and yet is key to the wall’s mechanical properties. To investigate the ultrastructure of the plant cell wall, we imaged the walls of onion (Allium cepa) bulbs in a near-native state via cryo-focused ion beam milling (cryo-FIB milling) and cryo-electron tomography (cryo-ET). This allowed the high-resolution visualization of cellulose fibers in situ. We reveal the coexistence of dense fiber fields bathed in a reticulated matrix we termed “meshing,” which is more abundant at the inner surface of the cell wall. The fibers adopted a regular bimodal angular distribution at all depths in the cell wall and bundled according to their orientation, creating layers within the cell wall. Concomitantly, employing homogalacturonan (HG)-specific enzymatic digestion, we observed changes in the meshing, suggesting that it is—at least in part—composed of HG pectins. We propose the following model for the construction of the abaxial epidermal primary cell wall: the cell deposits successive layers of cellulose fibers at −45° and +45° relative to the cell’s long axis and secretes the surrounding HG-rich meshing proximal to the plasma membrane, which then migrates to more distal regions of the cell wall.},
author = {Nicolas, William J. and Fäßler, Florian and Dutka, Przemysław and Schur, Florian KM and Jensen, Grant and Meyerowitz, Elliot},
issn = {0960-9822},
journal = {Current Biology},
keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology},
number = {11},
pages = {P2375--2389},
publisher = {Elsevier},
title = {{Cryo-electron tomography of the onion cell wall shows bimodally oriented cellulose fibers and reticulated homogalacturonan networks}},
doi = {10.1016/j.cub.2022.04.024},
volume = {32},
year = {2022},
}
@article{11373,
abstract = {The actin-homologue FtsA is essential for E. coli cell division, as it links FtsZ filaments in the Z-ring to transmembrane proteins. FtsA is thought to initiate cell constriction by switching from an inactive polymeric to an active monomeric conformation, which recruits downstream proteins and stabilizes the Z-ring. However, direct biochemical evidence for this mechanism is missing. Here, we use reconstitution experiments and quantitative fluorescence microscopy to study divisome activation in vitro. By comparing wild-type FtsA with FtsA R286W, we find that this hyperactive mutant outperforms FtsA WT in replicating FtsZ treadmilling dynamics, FtsZ filament stabilization and recruitment of FtsN. We could attribute these differences to a faster exchange and denser packing of FtsA R286W below FtsZ filaments. Using FRET microscopy, we also find that FtsN binding promotes FtsA self-interaction. We propose that in the active divisome FtsA and FtsN exist as a dynamic copolymer that follows treadmilling filaments of FtsZ.},
author = {Radler, Philipp and Baranova, Natalia S. and Dos Santos Caldas, Paulo R and Sommer, Christoph M and Lopez Pelegrin, Maria D and Michalik, David and Loose, Martin},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry},
publisher = {Springer Nature},
title = {{In vitro reconstitution of Escherichia coli divisome activation}},
doi = {10.1038/s41467-022-30301-y},
volume = {13},
year = {2022},
}
@article{11447,
abstract = {Empirical essays of fitness landscapes suggest that they may be rugged, that is having multiple fitness peaks. Such fitness landscapes, those that have multiple peaks, necessarily have special local structures, called reciprocal sign epistasis (Poelwijk et al. in J Theor Biol 272:141–144, 2011). Here, we investigate the quantitative relationship between the number of fitness peaks and the number of reciprocal sign epistatic interactions. Previously, it has been shown (Poelwijk et al. in J Theor Biol 272:141–144, 2011) that pairwise reciprocal sign epistasis is a necessary but not sufficient condition for the existence of multiple peaks. Applying discrete Morse theory, which to our knowledge has never been used in this context, we extend this result by giving the minimal number of reciprocal sign epistatic interactions required to create a given number of peaks.},
author = {Saona Urmeneta, Raimundo J and Kondrashov, Fyodor and Khudiakova, Kseniia},
issn = {1522-9602},
journal = {Bulletin of Mathematical Biology},
keywords = {Computational Theory and Mathematics, General Agricultural and Biological Sciences, Pharmacology, General Environmental Science, General Biochemistry, Genetics and Molecular Biology, General Mathematics, Immunology, General Neuroscience},
number = {8},
publisher = {Springer Nature},
title = {{Relation between the number of peaks and the number of reciprocal sign epistatic interactions}},
doi = {10.1007/s11538-022-01029-z},
volume = {84},
year = {2022},
}
@article{11448,
abstract = {Studies of protein fitness landscapes reveal biophysical constraints guiding protein evolution and empower prediction of functional proteins. However, generalisation of these findings is limited due to scarceness of systematic data on fitness landscapes of proteins with a defined evolutionary relationship. We characterized the fitness peaks of four orthologous fluorescent proteins with a broad range of sequence divergence. While two of the four studied fitness peaks were sharp, the other two were considerably flatter, being almost entirely free of epistatic interactions. Mutationally robust proteins, characterized by a flat fitness peak, were not optimal templates for machine-learning-driven protein design – instead, predictions were more accurate for fragile proteins with epistatic landscapes. Our work paves insights for practical application of fitness landscape heterogeneity in protein engineering.},
author = {Gonzalez Somermeyer, Louisa and Fleiss, Aubin and Mishin, Alexander S and Bozhanova, Nina G and Igolkina, Anna A and Meiler, Jens and Alaball Pujol, Maria-Elisenda and Putintseva, Ekaterina V and Sarkisyan, Karen S and Kondrashov, Fyodor},
issn = {2050-084X},
journal = {eLife},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
publisher = {eLife Sciences Publications},
title = {{Heterogeneity of the GFP fitness landscape and data-driven protein design}},
doi = {10.7554/elife.75842},
volume = {11},
year = {2022},
}
@article{11460,
abstract = {Background: Proper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous work demonstrated focal neuronal migration defects in mice carrying loss-of-function alleles of the recognized autism risk gene WDFY3. However, the cellular origins of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide critical insight into WDFY3-dependent disease pathology.
Methods: Here, in an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic analysis with double markers (MADM). MADM technology enabled us to genetically distinctly track and phenotypically analyze mutant and wild-type cells concomitantly in vivo using immunofluorescent techniques.
Results: We revealed a cell autonomous requirement of WDFY3 for accurate laminar positioning of cortical projection neurons and elimination of mispositioned cells during early postnatal life. In addition, we identified significant deviations in dendritic arborization, as well as synaptic density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant neurons in Wdfy3-MADM reporter mice at postnatal stages.
Limitations: While Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD pathology that remain inaccessible to investigation in humans, like most animal models, they do not a perfectly replicate all aspects of human ASD biology. The lack of human data makes it indeterminate whether morphological deviations described here apply to ASD patients or some of the other neurodevelopmental conditions associated with WDFY3 mutation.
Conclusions: Our genetic approach revealed several cell autonomous requirements of WDFY3 in neuronal development that could underlie the pathogenic mechanisms of WDFY3-related neurodevelopmental conditions. The results are also consistent with findings in other ASD animal models and patients and suggest an important role for WDFY3 in regulating neuronal function and interconnectivity in postnatal life.},
author = {Schaaf, Zachary A. and Tat, Lyvin and Cannizzaro, Noemi and Green, Ralph and Rülicke, Thomas and Hippenmeyer, Simon and Zarbalis, Konstantinos S.},
issn = {2040-2392},
journal = {Molecular Autism},
keywords = {Psychiatry and Mental health, Developmental Biology, Developmental Neuroscience, Molecular Biology},
publisher = {Springer Nature},
title = {{WDFY3 mutation alters laminar position and morphology of cortical neurons}},
doi = {10.1186/s13229-022-00508-3},
volume = {13},
year = {2022},
}