TY - JOUR AB - The superior colliculus (SC) in the mammalian midbrain is essential for multisensory integration and is composed of a rich diversity of excitatory and inhibitory neurons and glia. However, the developmental principles directing the generation of SC cell-type diversity are not understood. Here, we pursued systematic cell lineage tracing in silico and in vivo, preserving full spatial information, using genetic mosaic analysis with double markers (MADM)-based clonal analysis with single-cell sequencing (MADM-CloneSeq). The analysis of clonally related cell lineages revealed that radial glial progenitors (RGPs) in SC are exceptionally multipotent. Individual resident RGPs have the capacity to produce all excitatory and inhibitory SC neuron types, even at the stage of terminal division. While individual clonal units show no pre-defined cellular composition, the establishment of appropriate relative proportions of distinct neuronal types occurs in a PTEN-dependent manner. Collectively, our findings provide an inaugural framework at the single-RGP/-cell level of the mammalian SC ontogeny. AU - Cheung, Giselle T AU - Pauler, Florian AU - Koppensteiner, Peter AU - Krausgruber, Thomas AU - Streicher, Carmen AU - Schrammel, Martin AU - Özgen, Natalie Y AU - Ivec, Alexis AU - Bock, Christoph AU - Shigemoto, Ryuichi AU - Hippenmeyer, Simon ID - 12875 IS - 2 JF - Neuron SN - 0896-6273 TI - Multipotent progenitors instruct ontogeny of the superior colliculus VL - 112 ER - TY - JOUR AB - Poxviruses are among the largest double-stranded DNA viruses, with members such as variola virus, monkeypox virus and the vaccination strain vaccinia virus (VACV). Knowledge about the structural proteins that form the viral core has remained sparse. While major core proteins have been annotated via indirect experimental evidence, their structures have remained elusive and they could not be assigned to individual core features. Hence, which proteins constitute which layers of the core, such as the palisade layer and the inner core wall, has remained enigmatic. Here we show, using a multi-modal cryo-electron microscopy (cryo-EM) approach in combination with AlphaFold molecular modeling, that trimers formed by the cleavage product of VACV protein A10 are the key component of the palisade layer. This allows us to place previously obtained descriptions of protein interactions within the core wall into perspective and to provide a detailed model of poxvirus core architecture. Importantly, we show that interactions within A10 trimers are likely generalizable over members of orthopox- and parapoxviruses. AU - Datler, Julia AU - Hansen, Jesse AU - Thader, Andreas AU - Schlögl, Alois AU - Bauer, Lukas W AU - Hodirnau, Victor-Valentin AU - Schur, Florian KM ID - 14979 JF - Nature Structural & Molecular Biology KW - Molecular Biology KW - Structural Biology SN - 1545-9993 TI - Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores ER - TY - JOUR AB - Contraction and flow of the actin cell cortex have emerged as a common principle by which cells reorganize their cytoplasm and take shape. However, how these cortical flows interact with adjacent cytoplasmic components, changing their form and localization, and how this affects cytoplasmic organization and cell shape remains unclear. Here we show that in ascidian oocytes, the cooperative activities of cortical actomyosin flows and deformation of the adjacent mitochondria-rich myoplasm drive oocyte cytoplasmic reorganization and shape changes following fertilization. We show that vegetal-directed cortical actomyosin flows, established upon oocyte fertilization, lead to both the accumulation of cortical actin at the vegetal pole of the zygote and compression and local buckling of the adjacent elastic solid-like myoplasm layer due to friction forces generated at their interface. Once cortical flows have ceased, the multiple myoplasm buckles resolve into one larger buckle, which again drives the formation of the contraction pole—a protuberance of the zygote’s vegetal pole where maternal mRNAs accumulate. Thus, our findings reveal a mechanism where cortical actomyosin network flows determine cytoplasmic reorganization and cell shape by deforming adjacent cytoplasmic components through friction forces. AU - Caballero Mancebo, Silvia AU - Shinde, Rushikesh AU - Bolger-Munro, Madison AU - Peruzzo, Matilda AU - Szep, Gregory AU - Steccari, Irene AU - Labrousse Arias, David AU - Zheden, Vanessa AU - Merrin, Jack AU - Callan-Jones, Andrew AU - Voituriez, Raphaël AU - Heisenberg, Carl-Philipp J ID - 14846 JF - Nature Physics SN - 1745-2473 TI - Friction forces determine cytoplasmic reorganization and shape changes of ascidian oocytes upon fertilization ER - TY - THES AB - This thesis consists of four distinct pieces of work within theoretical biology, with two themes in common: the concept of optimization in biological systems, and the use of information-theoretic tools to quantify biological stochasticity and statistical uncertainty. Chapter 2 develops a statistical framework for studying biological systems which we believe to be optimized for a particular utility function, such as retinal neurons conveying information about visual stimuli. We formalize such beliefs as maximum-entropy Bayesian priors, constrained by the expected utility. We explore how such priors aid inference of system parameters with limited data and enable optimality hypothesis testing: is the utility higher than by chance? Chapter 3 examines the ultimate biological optimization process: evolution by natural selection. As some individuals survive and reproduce more successfully than others, populations evolve towards fitter genotypes and phenotypes. We formalize this as accumulation of genetic information, and use population genetics theory to study how much such information can be accumulated per generation and maintained in the face of random mutation and genetic drift. We identify the population size and fitness variance as the key quantities that control information accumulation and maintenance. Chapter 4 reuses the concept of genetic information from Chapter 3, but from a different perspective: we ask how much genetic information organisms actually need, in particular in the context of gene regulation. For example, how much information is needed to bind transcription factors at correct locations within the genome? Population genetics provides us with a refined answer: with an increasing population size, populations achieve higher fitness by maintaining more genetic information. Moreover, regulatory parameters experience selection pressure to optimize the fitness-information trade-off, i.e. minimize the information needed for a given fitness. This provides an evolutionary derivation of the optimization priors introduced in Chapter 2. Chapter 5 proves an upper bound on mutual information between a signal and a communication channel output (such as neural activity). Mutual information is an important utility measure for biological systems, but its practical use can be difficult due to the large dimensionality of many biological channels. Sometimes, a lower bound on mutual information is computed by replacing the high-dimensional channel outputs with decodes (signal estimates). Our result provides a corresponding upper bound, provided that the decodes are the maximum posterior estimates of the signal. AU - Hledik, Michal ID - 15020 KW - Theoretical biology KW - Optimality KW - Evolution KW - Information SN - 2663 - 337X TI - Genetic information and biological optimization ER - TY - GEN AB - Eva Benkova received a PhD in Biophysics at the Institute of Biophysics of the Czech Academy of Sciences in 1998. After working as a postdoc at the Max Planck Institute in Cologne and the Center for Plant Molecular Biology (ZMBP) in Tübingen, she became a group leader at the Plant Systems Biology Department of the Vlaams Instituut voor Biotechnologie (VIB) in Gent. In 2012, she transitioned to an Assistant Professor position at the Institute of Science and Technology Austria (ISTA) where she was later promoted to Professor. Since 2021, she has served as the Dean of the ISTA Graduate School. As a plant developmental biologist, she focuses on unraveling the molecular mechanisms and principles that underlie hormonal interactions in plants. In her current work, she explores the intricate connections between hormones and regulatory pathways that mediate the perception of environmental stimuli, including abiotic stress and nitrate availability. AU - Benková, Eva ID - 14842 IS - 1 T2 - Current Biology TI - Eva Benkova VL - 34 ER - TY - JOUR AB - GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing phasic release exhibits looser coupling distance than the tonic release. Furthermore, the tonic and phasic release are selectively affected by deletion of synaptoporin (SPO) and Ca 2+ -dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. The cytosolic protein CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane protein SPO, and they were colocalized in the same terminals. We developed the “Flash and Freeze-fracture” method, and revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP increase. Thus, we identified structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals. AU - Koppensteiner, Peter AU - Bhandari, Pradeep AU - Önal, Hüseyin C AU - Borges Merjane, Carolina AU - Le Monnier, Elodie AU - Roy, Utsa AU - Nakamura, Yukihiro AU - Sadakata, Tetsushi AU - Sanbo, Makoto AU - Hirabayashi, Masumi AU - Rhee, JeongSeop AU - Brose, Nils AU - Jonas, Peter M AU - Shigemoto, Ryuichi ID - 15084 IS - 8 JF - Proceedings of the National Academy of Sciences SN - 0027-8424 TI - GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles VL - 121 ER - TY - JOUR AB - Direct reciprocity is a powerful mechanism for cooperation in social dilemmas. The very logic of reciprocity, however, seems to require that individuals are symmetric, and that everyone has the same means to influence each others’ payoffs. Yet in many applications, individuals are asymmetric. Herein, we study the effect of asymmetry in linear public good games. Individuals may differ in their endowments (their ability to contribute to a public good) and in their productivities (how effective their contributions are). Given the individuals’ productivities, we ask which allocation of endowments is optimal for cooperation. To this end, we consider two notions of optimality. The first notion focuses on the resilience of cooperation. The respective endowment distribution ensures that full cooperation is feasible even under the most adverse conditions. The second notion focuses on efficiency. The corresponding endowment distribution maximizes group welfare. Using analytical methods, we fully characterize these two endowment distributions. This analysis reveals that both optimality notions favor some endowment inequality: More productive players ought to get higher endowments. Yet the two notions disagree on how unequal endowments are supposed to be. A focus on resilience results in less inequality. With additional simulations, we show that the optimal endowment allocation needs to account for both the resilience and the efficiency of cooperation. AU - Hübner, Valentin AU - Staab, Manuel AU - Hilbe, Christian AU - Chatterjee, Krishnendu AU - Kleshnina, Maria ID - 15083 IS - 10 JF - Proceedings of the National Academy of Sciences SN - 0027-8424 TI - Efficiency and resilience of cooperation in asymmetric social dilemmas VL - 121 ER - TY - GEN AB - in the research article "Efficiency and resilience of cooperation in asymmetric social dilemmas" (by Valentin Hübner, Manuel Staab, Christian Hilbe, Krishnendu Chatterjee, and Maria Kleshnina). We used different implementations for the case of two and three players, both described below. AU - Hübner, Valentin AU - Kleshnina, Maria ID - 15108 TI - Computer code for "Efficiency and resilience of cooperation in asymmetric social dilemmas" ER - TY - JOUR AB - Global storm-resolving models (GSRMs) use strongly refined horizontal grids compared with the climate models typically used in the Coupled Model Intercomparison Project (CMIP) but employ comparable vertical grid spacings. Here, we study how changes in the vertical grid spacing and adjustments to the integration time step affect the basic climate quantities simulated by the ICON-Sapphire atmospheric GSRM. Simulations are performed over a 45 d period for five different vertical grids with between 55 and 540 vertical layers and maximum tropospheric vertical grid spacings of between 800 and 50 m, respectively. The effects of changes in the vertical grid spacing are compared with the effects of reducing the horizontal grid spacing from 5 to 2.5 km. For most of the quantities considered, halving the vertical grid spacing has a smaller effect than halving the horizontal grid spacing, but it is not negligible. Each halving of the vertical grid spacing, along with the necessary reductions in time step length, increases cloud liquid water by about 7 %, compared with an approximate 16 % decrease for halving the horizontal grid spacing. The effect is due to both the vertical grid refinement and the time step reduction. There is no tendency toward convergence in the range of grid spacings tested here. The cloud ice amount also increases with a refinement in the vertical grid, but it is hardly affected by the time step length and does show a tendency to converge. While the effect on shortwave radiation is globally dominated by the altered reflection due to the change in the cloud liquid water content, the effect on longwave radiation is more difficult to interpret because changes in the cloud ice concentration and cloud fraction are anticorrelated in some regions. The simulations show that using a maximum tropospheric vertical grid spacing larger than 400 m would increase the truncation error strongly. Computing time investments in a further vertical grid refinement can affect the truncation errors of GSRMs similarly to comparable investments in horizontal refinement, because halving the vertical grid spacing is generally cheaper than halving the horizontal grid spacing. However, convergence of boundary layer cloud properties cannot be expected, even for the smallest maximum tropospheric grid spacing of 50 m used in this study. AU - Schmidt, Hauke AU - Rast, Sebastian AU - Bao, Jiawei AU - Cassim, Amrit AU - Fang, Shih Wei AU - Jimenez-De La Cuesta, Diego AU - Keil, Paul AU - Kluft, Lukas AU - Kroll, Clarissa AU - Lang, Theresa AU - Niemeier, Ulrike AU - Schneidereit, Andrea AU - Williams, Andrew I.L. AU - Stevens, Bjorn ID - 15097 IS - 4 JF - Geoscientific Model Development SN - 1991-959X TI - Effects of vertical grid spacing on the climate simulated in the ICON-Sapphire global storm-resolving model VL - 17 ER - TY - JOUR AB - In this note, we prove a formula for the cancellation exponent kv,n between division polynomials ψn and ϕn associated with a sequence {nP}n∈N of points on an elliptic curve E defined over a discrete valuation field K. The formula greatly generalizes the previously known special cases and treats also the case of non-standard Kodaira types for non-perfect residue fields. AU - Naskręcki, Bartosz AU - Verzobio, Matteo ID - 12311 JF - Proceedings of the Royal Society of Edinburgh Section A: Mathematics KW - Elliptic curves KW - Néron models KW - division polynomials KW - height functions KW - discrete valuation rings SN - 0308-2105 TI - Common valuations of division polynomials ER -