Biology subjects

Geiger, L. T.

Publications and source records attributed to Geiger, L. T..

7 recordsLinked to original sources

bioRxiv2026

Terminal selector and subtype selector function across 200 million years of nematode evolution

The evolution of brains is subject to investigation in many different animal groups, each offering unique advantages to advance our understanding of the cellular, molecular and regulatory substrates of evolutionary change. Here, we use two nematode species, C. elegans and P. pacificus, separated by more than 200 million years of evolution to explore how neuronal cell types and the regulatory programs instructing the identity of these cell types have evolved over time. Using gene expression pattern analysis, we compare the differentiation programs of over half of all nematode neuron classes. To explore how the gene regulatory architecture of neuronal differentiation programs evolves, we apply our deep understanding of neuronal differentiation programs, controlled by terminal selectors and subtype selectors in C. elegans. Through mutant analysis of orthologous P. pacificus regulatory factors, we elucidate patterns of conservation and novelties over such substantial evolutionary distance. We discovered striking similarities in terminal selector expression and activities throughout the nervous system but also observed that terminal selectors can acquire novel sites of expression and distinct regulatory capabilities, manifested by changes in effector gene expression and, hence, neuronal phenotypes. Our mutant analysis argues for a buffering of terminal selector function and for an evolutionary lability of differences in closely related neuronal subtypes. Taken together, our analysis reveals molecular substrates of evolutionary change in nervous systems.

neuroscience↗

bioRxiv2026

Coexistence of phasmid sensory neurons and caudal glands offers a new perspective on cell type evolution in nematodes

The highly conserved body plan of nematodes makes members of this phylum excellent models to study cell type evolution. Early branching nematode lineages, mostly occupying aquatic habitats, usually contain caudal glands deployed for underwater attachment to a substrate, but have been thought to lack phasmid sensory organs, resulting in their historical classification as "Aphasmidia". With the transition to a terrestrial environment, nematodes lost caudal glands and gained phasmid sensory neurons. The supposed mutually exclusive existence of caudal glands and phasmids has led to the suggestion that phasmid neurons may have evolved from caudal glands. Here, we rule out this possibility through light and electron microscopical analysis of Mononchus aquaticus, a member of the early branching Dorylaimia lineage, showing that phasmid sensory neurons and caudal glands do coexist. This observation not only argues against a proposed cell type evolution scenario accompanying aquatic-to-terrestrial transitions but also indicates that the presence of phasmid sensory organs may have been an ancestral trait of the nematode phylum.

evolutionary biology↗

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↗

bioRxiv2025

Identity and functions of monoaminergic neurons in the predatory nematode Pristionchus pacificus reveal nervous system conservation and divergence

Changes in neurotransmitter usage in homologous neurons may drive evolutionary adaptations in neural circuits across animal phylogeny. The predatory nematode Pristionchus pacificus can be used as a model system to examine nervous system evolution by comparing neurotransmitter expression with that of C. elegans and other nematodes. Here we characterize P. pacificus neurotransmitter expression and function in specific neurons, focusing on its complete set of monoaminergic neurons. We discover patterns of conservation as well as novelties. We examine the roles of monoamines in specific behaviors using neurotransmitter synthesis and vesicular transporter mutants, finding possible differences in the control of host-finding and dispersal behavior.

neuroscience↗

bioRxiv2024

Molecular patterns of evolutionary changes throughout the whole nervous system of multiple nematode species

One avenue to better understand brain evolution is to map molecular patterns of evolutionary changes in neuronal cell types across entire nervous systems of distantly related species. Generating whole-animal single-cell transcriptomes of three nematode species from the Caenorhabditis genus, we observed a remarkable stability of neuronal cell type identities over more than 45 million years of evolution. Conserved patterns of combinatorial expression of homeodomain transcription factors are among the best classifiers of homologous neuron classes. Unexpectedly, we discover an extensive divergence in neuronal signaling pathways. While identities of neurotransmitter-producing neurons (glutamate, acetylcholine, GABA and several monoamines) remain stable, ionotropic and metabotropic receptors for all these neurotransmitter systems show substantial divergence, resulting in more than half of all neuron classes changing their capacity to be receptive to specific neurotransmitters. Neuropeptidergic signaling is also remarkably divergent, both at the level of neuropeptide expression and receptor expression, yet the overall dense network topology of the wireless neuropeptidergic connectome remains stable. Novel neuronal signaling pathways are suggested by our discovery of small secreted proteins that show no obvious hallmarks of conventional neuropeptides, but show similar patterns of highly neuron-type-specific and highly evolvable expression profiles. In conclusion, by investigating the evolution of entire nervous systems at the resolution of single neuron classes, we uncover patterns that may reflect basic principles governing evolutionary novelty in neuronal circuits.

evolutionary biology↗

bioRxiv2024

Early-life stress alters chromatin modifications in VTA to prime stress sensitivity

Early-life stress increases sensitivity to subsequent stress, which has been observed at behavioral, neural activity, and gene expression levels. However, the molecular mechanisms underlying such long-lasting sensitivity are poorly understood. We tested the hypothesis that persistent changes in transcription and transcriptional potential were maintained at the level of the epigenome, through changes in chromatin. We used a combination of bottom-up mass spectrometry, viral-mediated epigenome-editing, RNA-sequencing, patch clamp electrophysiology of dopamine neurons, and behavioral quantification in a mouse model of early-life stress, focusing on the ventral tegmental area (VTA), a dopaminergic brain region critically implicated in motivation, reward learning, stress response, and mood and drug disorders. We found that early-life stress alters histone dynamics in VTA, including enrichment of histone-3 lysine-4 monomethylation -- associated with open chromatin and primed or active enhancers -- and the H3K4 monomethylase Setd7. Mimicking early-life stress through postnatal overexpression of Setd7 and enrichment of H3K4me1 in VTA sensitizes transcriptional, physiological, and behavioral response to adult stress. These findings link early-life stress experience to long-term stress hypersensitivity within the brains dopaminergic circuitry, providing a mechanism by which early-life stress increases risk for mood and anxiety disorders later in life.

neuroscience↗

bioRxiv2022

Pain as a Trigger for Epigenetic Modifications in Limbic Circuitry

Chronic pain involves both central and peripheral neuronal plasticity that encompasses changes in the brain, spinal cord, and peripheral nociceptors. Within the forebrain, mesocorticolimbic regions associated with emotional regulation have recently been shown to exhibit enduring gene expression changes in models of chronic pain. To better understand how such enduring transcriptional changes might be regulated within brain structures associated with processing of pain or affect, we examined epigenetic modifications associated with active or permissive transcriptional states (histone H3 lysine 4 mono and trimethylation, and histone H3 lysine 27 acetylation) in periaqueductal gray, lateral hypothalamus, nucleus accumbens, and ventral tegmental area five weeks after sciatic nerve injury to model chronic pain. For mice in chronic pain, we observed an overall trend for a reduction of these epigenetic markers in the periaqueductal gray, lateral hypothalamus, and nucleus accumbens, but not the ventral tegmental area. Moreover, we discovered that some epigenetic modifications exhibited changes associated with pain history, while others were associated with individual differences in pain sensitivity. When taken together, these results suggest that chronic pain may lead to a suppression of transcription and gene expression in key limbic brain structures and circuits, which may ultimately result in maladaptive plasticity within these systems.

neuroscience↗