Biology subjects

Naumann, H.

Publications and source records attributed to Naumann, H..

5 recordsLinked to original sources

bioRxiv2026

Large-scale endoplasmic reticulum membrane solidification spatially organizes proteins under thermal or metabolic stress

Organelle homeostasis is a key determinant of cellular fitness, yet how cells remodel their membranes in response to environmental change remains unclear. Here, we identify a temperature- and lipid saturation-dependent transformation of endoplasmic reticulum membranes into giant, rigid, multilamellar tubes in cells and in vivo. These rods emerge from demixing of saturated lipids into solid-like domains - a previously unrecognised, large-scale endomembrane phase behaviour, fundamentally distinct from the transient liquid-ordered nanodomains of the plasma membrane. ER-tubulating reticulon-homology proteins are excluded from rods; their segregation drives progressive membrane flattening and ultimately multilayered wrapping. Surfactant-producing alveolar type-II lung cells, enriched in saturated lipids, form rods even at 37{degrees}C, demonstrating that native lipid metabolism can induce this transformation. This spatially organizing lipid-protein domain interplay may tune the ER tubule/sheet balance and provide a homeoviscous mechanism to preserve fluidity in the cholesterol-poor ER under thermal or metabolic stress.

cell biology↗

bioRxiv2025

An RNA ligase shapes transcriptional profiles, neural function, and behaviour in the developing larval zebrafish

RNA ligases are essential for the repair, splicing, and editing of RNA across various biological systems. Recently, a new enzyme that catalyses 5-3 RNA ligation - RNA ligase 1 (Rlig1) - was identified in vitro. However, the in vivo biological functions of Rlig1 have remained elusive. Here, we reveal the role of Rlig1 during vertebrate development using embryonic and larval zebrafish as a model system. We found that rlig1 mRNA is maternally deposited and present ubiquitously during early embryogenesis, whereas at larval stages it localises to the brain and eyes. Interestingly, CRISPR/Cas9-generated rlig1 knockout zebrafish exhibited no overt morphological abnormalities, but showed reduced behavioural responsiveness to visual stimuli along with massively perturbed transcriptomes and widespread dysregulation of core metabolic and translational pathways. Brain-wide calcium imaging in rlig1 knockout larvae revealed decreased neuronal activity in key regions for visual processing, consistent with the observed behavioural defects. Together, our findings identify a role for Rlig1 in maintaining the integrity and function of the nervous system and uncover a new link between neuronal RNA processing, development, and sensory-motor computation.

developmental biology↗

bioRxiv2025

Parallel and convergent pathways for multifeature visual processing in larval zebrafish sensorimotor decision-making

Animals continuously extract and evaluate diverse sensory information from the environment to guide behavior. Yet, how neural circuits integrate multiple, potentially conflicting, inputs during decision-making remains poorly understood. Here, we use larval zebrafish to address this question, leveraging their robust optomotor response to coherent random dot motion and phototaxis towards light. We demonstrate that animals employ an additive behavioral algorithm of three visual features: motion coherence, luminance level, and changes in luminance. Using brain-wide two-photon imaging, we identify the loci of these computations, with the anterior hindbrain emerging as a multifeature sensory integration hub. Through single-cell neurotransmitter and morphological analyses of functionally identified neurons, we characterize potential connections within and across computational nodes. These experiments reveal three parallel and converging pathways, matching our behavioral results. Our study provides a mechanistic brain-wide account of how a vertebrate brain integrates multiple features to drive sensorimotor decisions, bridging the algorithmic bases of behavior and its neural implementation.

neuroscience↗

bioRxiv2025

Correlative light and electron microscopy reveals the fine circuit structure underlying evidence accumulation in larval zebrafish

AbstractEvidence accumulation is a fundamental neural computation essential for adaptive behavior, yet its synaptic implementation remains unclear. Addressing this challenge critically depends on linking neural dynamics to circuit structure within the same brain. Here, we combine functional calcium imaging with large-scale ultrastructural electron microscopy (EM) to uncover the wiring logic of visual evidence accumulation in larval zebrafish. In a functionally imaged EM dataset of the anterior hindbrain, we identify conserved morphological cell types whose activity patterns define distinct computational roles. Bilateral inhibition, disinhibition, and recurrent connectivity emerge as key circuit motifs shaping these dynamics. To generalize our findings across animals, we develop a photoconversion-based pipeline to label and reconstruct functionally characterized neurons, enabling us to train a classifier that predicts functional identity from morphology alone. Applying this classifier to a second, whole-brain EM dataset lacking functional data reveals matching connectivity patterns, significantly augmenting its applicability for detailed circuit dissections. Based on these results, we develop and constrain a biophysically realistic neural network model that captures observed dynamics and yields predictions we tested and confirmed experimentally. Our work illustrates how hypothesis-driven connectomics can uncover the synaptic basis of sensory-motor computations and establishes a novel framework for cross-animal circuit dissection in the vertebrate brain.

neuroscience↗

bioRxiv2024

Transcriptional Dosage of Oncogenic KRAS Drives Lung Adenocarcinoma Cell States, Progression and Metastasis

Cancer cells display distinct, recurrent phenotypic cell states. Metastatic spreading correlates with tumor cell state evolution. However, the molecular mechanisms underlying metastasis remain elusive. Here, we demonstrate that the quantitative dosage of oncogenic KRAS drives lung adenocarcinoma progression and metastasis via the integration of external signaling and pioneer transcription factor dynamics into qualitative cell states. Combining mouse models, in vivo CRISPR activation screens, and fate mapping, we show that even mild transcriptional amplification of KRAS significantly fuels tumor progression and metastasis. Chromatin profiling and transcriptomics reveal that high and low KRAS dosages supersede and integrate inflammatory and TGF{beta} signaling to dictate mouse cancer cell states. Patient data show that KRAS dosages correlate with distinct survival outcomes, transcription factor activity, and cell states. Direct KRAS inhibition in xenografts limits the KRAS-high "proliferative" cell state but spares a minimal residual state mimicking the KRAS-low "ciliated-like" state. Thus, oncogenic KRAS dosage fuels tumor heterogeneity at the cell state level and drives a bimodal tumor evolution during metastasis, with implications for prognosis and treatment.

cancer biology↗