Biology subjects

Tosches, M. A.

Publications and source records attributed to Tosches, M. A..

11 recordsLinked to original sources

bioRxiv2026

Cell-type Plasticity Supports Behavioral Adaptations at the Water-to-Land Interface

Animals inhabiting aquatic or terrestrial habitats experience different constraints on their physiology and locomotion, and are exposed to fundamentally different sensory environments. Across evolutionary timescales, most species have adapted to live exclusively either in water or on land. Newts are among the vertebrates that defy this rule and split their adult lives between freshwater ponds and terrestrial habitats. In these amphibians, transitions across environments cause remarkable phenotypic plasticity in their body morphology. But whether and how the nervous system and behavior also adapt to these environmental changes remains poorly explored. Here, we establish the Iberian ribbed newt Pleurodeles waltl as a new model to study the neurobiology of environmental plasticity in a vertebrate. We first show that experimental transitions between aquatic and terrestrial laboratory settings recapitulate morphological changes observed in the wild. Furthermore, aquatic and terrestrial newts display plasticity in sensory and motor behaviors, including differences in walking gait and odor responsiveness. In the olfactory system, the transition from water to land involves a profound remodeling of the nasal epithelium, including reversible transcriptomic changes in secretory and support cells, and an increase of neurogenesis. Together, our findings reveal how plasticity of specific cell types in the nervous system supports behavioral adaptations across environments. More broadly, this work establishes newts as a model to study the functional constraints and convergent adaptations that may have shaped the evolution of vertebrate nervous systems in water and on land.

neuroscience↗

bioRxiv2026

Glial cell states bias the regeneration of neuron types across the newt life cycle

Salamanders have outstanding regenerative abilities, which tend to decline in post-metamorphic life stages. Among various tissues, these amphibians can regenerate the brain from ependymoglia cells, an adult neural stem cell population. Ependymoglia cells are heterogeneous; yet, whether ependymoglia cell diversity underlies variation of regenerative capacity across brain regions and life cycle stages remains poorly studied. Here we present a cell type comparison of regeneration in the pallium (dorsal telencephalon) of pre- and post-metamorphic newts. We found that ependymoglia cells exist in a continuum of cell states ranging from active proliferation to quiescence across life cycle stages, with a deep quiescence state featuring expression of mammalian astrocyte genes. Ependymoglia cell state changes are associated with a slower onset of proliferation and neurogenesis in post-metamorphic animals. Comparisons with developmental and adult neurogenesis reveal that pallial ependymoglia cells retain regional restrictions but can override temporal fate restrictions in response to an injury, producing neurons that are normally born only in early development. We thus find that brain regeneration in newts is not a simple amplification of adult neurogenesis, but a distinct process where the initial molecular state of ependymoglia cells biases the relative proportions of regenerated neuron types. Our findings establish post-metamorphic newts as a system to study how astrocyte-like glial cells can activate a neurogenic program in response to brain injury.

developmental biology↗

bioRxiv2025

Hybrid Solid-Liquid Optics Enable Scalable, High-Resolution, Multi-Immersion Light-Sheet Microscopy

Modern biology increasingly depends on data-driven discovery, requiring scalable and affordable high-content 3D imaging across molecular to organ scales. Although tissue clearing, expansion microscopy, and light-sheet microscopy (LSM) enable subcellular-resolution imaging of intact specimens, their scalability remains fundamentally limited by detection optics: immersion objectives deliver high-resolution, aberration-free imaging but with short working distances, high cost, and multi-immersion incompatibility, while air objectives offer long working distances and portability at lower cost but suffer from severe aberrations and reduced photon collection when imaging immersed samples. We introduce the Hybrid Solid-Liquid Immersion Lens (HySIL) framework, which pairs an off-the-shelf solid optical component with a refractive index-matched liquid to precompensate aberrations and enhance resolution. Building on HySIL, we developed SCOPE and Super-SCOPE, objective-agnostic imaging devices achieving submicron lateral resolution (<0.75 {micro}m) across centimeter-scale samples using inexpensive air objectives with >30 mm working distances. Integration with a low-cost LSM platform yielded a compact, scalable system demonstrated for multi-immersion, multi-color, subcellular-resolution mapping of cleared or expanded mouse, salamander, and cavefish brains, human iPSC-derived organoids, and 3D histopathology of breast tissue. HySIL and SCOPE establish an accessible foundation for scalable, high-resolution volumetric imaging, advancing data-driven biological discovery.

bioengineering↗

bioRxiv2025

A conserved logic for the development of cortical layering in tetrapods

The cerebral cortex is part of the pallium, a brain region conserved across vertebrates yet remarkably diverse in structure and cellular composition. A defining feature of the cerebral cortex is its organization into neuronal layers with distinct gene expression profiles, input-output connectivity, and function. According to prevailing models, the cerebral cortex emerged in ancestral amniotes (mammals and reptiles) following innovations in pallial development that enabled the generation of diverse neuron types and their laminar organization.1-11 However, little is known about pallial development and architecture in amphibians, the sister group of amniotes. Here we show that in the salamander Pleurodeles waltl, the dorsal pallium is organized in distinct superficial and deep layers with neurons that develop following cellular and molecular principles of mammalian corticogenesis. Using birthdating analysis, barcode-based lineage tracing, and single-cell RNA sequencing, we find that radial glia temporal states and intermediate progenitor cells are conserved across species, while neuronal differentiation trajectories are highly evolvable. Neurons generated at different developmental time points occupy different layers and exhibit distinct molecular and projection identities. Thus, temporally-patterned neurogenesis represents an ancient organizing principle of layered pallia, although mammals display an inverted layer order along the radial axis. Together, these findings demonstrate that the core developmental principles underlying cortical layering - including temporal patterning, intermediate progenitors, and laminar organization - predate the origin of amniotes. Our results suggest that the evolutionary expansion of the mammalian neocortex built upon a deeply conserved developmental framework already present in early tetrapods.

developmental biology↗

bioRxiv2025

Evolution of Cajal-Retzius Cells in Vertebrates from an Ancient Class of Tp73+ Neurons

Evolutionary changes of cortical development were instrumental for the emergence of the mammalian neocortex. Cajal-Retzius cells, a transient neuron type discovered over a century ago, are critical players in the development of mammalian-specific cortical features such as inside-out corticogenesis. However, it is unclear whether Cajal-Retzius cells exist only in mammals, or if they are ancestral in vertebrates but acquired new functions during mammalian brain development. To trace the evolution of this cell type, we probe the presence of Cajal-Retzius cells in chicken, salamander, zebrafish, and little skate. First, through comparative transcriptomics and spatial analysis we show that Cajal-Retzius cells are conserved in vertebrates. However, only amniote Cajal-Retzius cells gained robust expression of Reelin, a secreted glycoprotein crucial for mammalian cortical development. Second, we find that Cajal-Retzius cells are part of a larger and diverse family of neuron types, and are closely related to Tp73+ external tufted cells in the olfactory bulb, which express most of the "canonical" Cajal-Retzius transcription factors. Our results indicate that Cajal-Retzius cells emerged early in vertebrate history, using a regulatory program largely shared with neurons in the olfactory system, and that transcriptomic novelties underlie their specialized roles in mammalian cortical development. This is an extreme example of how cell types may diverge in morphology and function over the course of evolution even when their core transcriptomic profile is broadly preserved.

neuroscience↗

bioRxiv2024

Adeno-Associated Viral Tools to Trace Neural Development and Connectivity Across Amphibians

The development, evolution, and function of the vertebrate central nervous system (CNS) can be best studied using diverse model organisms. Amphibians, with their unique phylogenetic position at the transition between aquatic and terrestrial lifestyles, are valuable for understanding the origin and evolution of the tetrapod brain and spinal cord. Their metamorphic developmental transitions and unique regenerative abilities also facilitate the discovery of mechanisms for neural circuit remodeling and replacement. The genetic toolkit for amphibians, however, remains limited, with only a few species having sequenced genomes and a small number of transgenic lines available. In mammals, recombinant adeno-associated viral vectors (AAVs) have become a powerful alternative to genome modification for visualizing and perturbing the nervous system. AAVs are DNA viruses that enable neuronal transduction in both developing and adult animals with low toxicity and spatial, temporal, and cell-type specificity. However, AAVs have never been shown to transduce amphibian cells efficiently. To bridge this gap, we established a simple, scalable, and robust strategy to screen AAV serotypes in three distantly-related amphibian species: the frogs Xenopus laevis and Pelophylax bedriagae, and the salamander Pleurodeles waltl, in both developing larval tadpoles and post-metamorphic animals. For each species, we successfully identified at least two AAV serotypes capable of infecting the CNS; however, no pan-amphibian serotype was identified, indicating rapid evolution of AAV tropism. In addition, we developed an AAV-based strategy that targets isochronic cohorts of developing neurons - a critical tool for parsing neural circuit assembly. Finally, to enable visualization and manipulation of neural circuits, we identified AAV variants for retrograde tracing of neuronal projections in adult animals. Our findings expand the toolkit for amphibians to include AAVs, establish a generalizable workflow for AAV screening in non-canonical research organisms, generate testable hypotheses for the evolution of AAV tropism, and lay the foundation for modern cross-species comparisons of vertebrate CNS development, function, and evolution.

neuroscience↗

bioRxiv2023

Mammalian olfactory cortex neurons retain molecular signatures of ancestral cell types

The cerebral cortex diversified extensively during vertebrate evolution. Intriguingly, the three-layered mammalian olfactory cortex resembles the cortical cytoarchitecture of non-mammals yet evolved alongside the six-layered neocortex, enabling unique comparisons for investigating cortical neuron diversification. We performed single-nucleus multiome sequencing across mouse three- to six-layered cortices and compared neuron types across mice, reptiles and salamander. We identified neurons that are olfactory cortex-specific or conserved across mouse cortical areas. However, transcriptomically similar neurons exhibited area-specific epigenetic states. Additionally, the olfactory cortex showed transcriptomic divergence between lab and wild-derived mice, suggesting enhanced circuit plasticity through adult immature neurons. Finally, olfactory cortex neurons displayed marked transcriptomic similarities to reptile and salamander neurons. Together, these data indicate that the mammalian olfactory cortex retains molecular signatures representative of ancestral cortical traits.

neuroscience↗

bioRxiv2022

Glutamatergic neuron types in the amygdala of the urodele amphibian Pleurodeles waltl

The amygdala is a complex brain structure in the vertebrate telencephalon, essential for regulating social behaviors, emotions and (social) cognition. In contrast to the vast majority of neuron types described in the many nuclei of the mammalian amygdala, little is known about the neuronal diversity in non-mammals, making reconstruction of its evolution particularly difficult. Here, we characterize glutamatergic neuron types in the amygdala of the salamander Pleurodeles waltl. Our single-cell RNA sequencing data indicate the existence of at least ten distinct types and subtypes of glutamatergic neurons in the salamander amygdala. In situ hybridization for marker genes indicates that these neuron types are located in three major subdivisions: the lateral amygdala, the medial amygdala, and a newly-defined area demarcated by high expression of the transcription factor Sim1. The gene expression profiles of these neuron types suggest similarities with specific neuron types in the sauropsid and mammalian amygdala, and in particular the evolutionary conservation of Sim1-expressing amygdalar neurons in tetrapods. Taken together, our results reveal a surprising diversity of glutamatergic neuron types in the amygdala of salamanders, despite the anatomical simplicity of their brain.

neuroscience↗

bioRxiv2022

Cell type profiling in salamanders identifies innovations in vertebrate forebrain evolution

The evolution of advanced cognition in vertebrates is associated with two independent innovations in the forebrain: the six-layered neocortex in mammals and the dorsal ventricular ridge (DVR) in sauropsids (reptiles and birds). How these novelties arose in vertebrate ancestors remains unclear. To reconstruct forebrain evolution in tetrapods, we built a cell type atlas of the telencephalon of the salamander Pleurodeles waltl. Our molecular, developmental, and connectivity data indicate that parts of the sauropsid DVR trace back to tetrapod ancestors. In contrast, the salamander dorsal pallium is devoid of cellular and molecular characteristics of the mammalian neocortex, yet shares similarities with entorhinal cortex and subiculum. Our findings chart the series of innovations that resulted in the emergence of the sauropsid DVR, and the mammalian six-layered neocortex.

neuroscience↗

bioRxiv2020

Spatial tissue profiling by imaging-free molecular tomography

Genomics techniques are currently being adapted to provide spatially resolved omics profiling. However, the adaptation of each new method typically requires the setup of specific detection strategies or specialized instrumentation. A generic approach to spatially resolve different types of high throughput data is missing. Here, we describe an imaging-free framework to localize high throughput readouts within a tissue by combining compressive sampling and image reconstruction. We implemented this framework to transform a low-input RNA sequencing protocol into an imaging-free spatial transcriptomics technique (STRP-seq) and validated this method with a transcriptome profiling of the murine brain. To verify the broad applicability of STRP-seq, we applied the technique on the brain of the Australian bearded dragon Pogona vitticeps. Our results reveal the molecular anatomy of the telencephalon of this lizard, providing evidence for a marked regionalization of the reptilian pallium and subpallium. Overall, the proposed framework constitutes a new approach that allows upgrading in a generic fashion conventional genomic assays to spatially resolved techniques.

genomics↗

bioRxiv2018

From spiral cleavage to bilateral symmetry: The developmental cell lineage of the annelid brain

The spiral cleavage pattern is characteristic for Spiralia (Lophotrochozoa), a large assembly of marine invertebrates. In most cases, spiral cleavage produces freely swimming, trochophora-type larvae with a simple nervous system that controls ciliary locomotion. These larvae acquire bilateral symmetry, as manifested for example in the larval brain. The transition from the rotational symmetry of spiral cleavage into the bilateral adult body has not yet been understood. Here, we present the developmental cell lineage of the brain of the annelid Platynereis dumerilii from the zygote until the mid-trochophore stage (~30 hpf), in combination with a gene expression atlas for several embryonic and larval stages. Comparison of multiple embryos reveals a highly stereotypical development and an invariant cell lineage of the differentiated cell types. In addition, we observe a fundamental subdivision of the larval brain into a highly proliferative dorsolateral region and an early differentiating ventromedial region that gives rise to the apical nervous system. The transition from rotational to bilateral symmetry progresses gradually from the lateral to the central regions. Strikingly, the spiral-to-bilateral transition does not involve extensive cell migration. Rather, corresponding cells in different spiral quadrants acquire highly divergent identities in line with their bilateral position.

developmental biology↗