Biology subjects

Foster, W.

Publications and source records attributed to Foster, W..

15 recordsLinked to original sources

bioRxiv2026

Spontaneous behavior predicts colony membership, individual identity, and rank in naked mole-rat societies

Animal societies are organized across scales, from moment-to-moment actions of individuals to dynamic group structure. A central challenge in sociobiology is to understand how behaviors of individuals shape group structure. Here, using machine vision to map recurrent fine-scale behavioral modules in the eusocial naked mole-rat (Heterocephalus glaber), we show that spontaneous behavior in isolation predicts group-level social organization, including colony membership and individual identity. We determined dominance relationships and found highly linear hierarchies, with ranks stable over months to years. Remarkably, fine-scale behavioral profiles in isolation correctly predicted pairwise dominance relationships, allowing reconstruction of rank order within each colony. Models trained within one colony predicted rank poorly in others, suggesting that naked mole-rats express social position through behavioral patterns specific to each colony. Together, our results connect fine-scale behavior to social structure maintained over years and show that, even when an animal is alone, its behavior carries signatures of its identity, colony, and place within that society.

animal behavior and cognition↗

bioRxiv2026

The Greatwall/PP2A-B55α axis remodels the G2/M boundary and shapes cellular dependence on PKMYT1

The switch-like G2/M transition and mitotic exit depend on a feedback loop comprising CDK1, Greatwall kinase, and the PP2A-B55 phosphatase. Monogenic disruptions of these regulators impair cellular functions, drive genomic instability, and promote cancer-associated characteristics. Yet how perturbations of this feedback loop interact, and whether their effects depend on cellular context, remain unclear. Here, we assess how combinatorial perturbations of CDK1, Greatwall, and PP2A-B55 affect cell-cycle control in non-transformed RPE-1 and tumour-derived HeLa cells. We identify PP2A-B55 as a context-dependent G2/M repressor with a critical role in cancer cells, where it cooperates with PKMYT1 and, to a lesser extent, WEE1 to prevent premature mitosis. In cancer cells, but not in non-transformed cells, reduced PP2A-B55 activity and Greatwall overexpression produce marked sensitisation to the PKMYT1-selective RP-6306 and modest sensitisation to the WEE1-selective adavosertib. This asymmetric sensitisation reflects a functional separation between WEE1 and PKMYT1 in S- and G2-phase control. Our work outlines fundamental and cell-type-specific contributions of CDK1, Greatwall and PP2A-B55 to cell-cycle regulation and proposes G2/M plasticity as a vulnerability with utility in PKMYT1-targeted therapy.

cell biology↗

bioRxiv2026

Muscle Loss as a Foundational Step in the Development and Evolution of the Turtle Shell

Modern biodiversity is built on a series of disparate body plans whose origins are obscured by deep time. Our most direct source of clarifying data is the fossilized skeleton, where morphology reflects an evolving functionality realized through the development of associated tissues. We apply this dualistic perspective to the shelled body plan of turtles whose Paleozoic initiation is marked by a derived relationship between ribs and dermis (Lyson & Bever, 2020). Current developmental models remain in conflict with an increasingly informative fossil record, suggesting critical steps remain unrecognized. Here we explore the hypothesis that the breakdown of rib-spanning muscles--an evolutionary transformation mirrored in embryogenesis--is one such step. Multi-modal imaging of turtle embryos, including a novel application of histology-based deep learning (Kiemen et al., 2022; Matos-Romero et al., 2025; Forjaz et al., 2026), establishes intercostal muscle degradation as preceding turtle-specific rib development and highlights the heuristic power of 3D, whole-embryo analysis (Forjaz et al., 2026). Quantified divergence from mouse pinpoints the timing and tempo of this organized, apoptotic breakdown. Initial evidence suggests an associated non-pathological inflammatory response, which has been shown capable of driving evolutionarily stable hyperossification (Rashid et al., 2023). These patterns support trunk muscles as a critical signalling centre whose ontogenetic loss set the phylogenetic stage for a morphogenetic transformation remarkable in a non-metamorphic species.

evolutionary biology↗

bioRxiv2026

Whole organism 3D mapping reveals universal branching topology and biophysical optimization governs vascular and nervous system development

The vascular and nervous systems are transport networks essential for life, yet whether universal geometric and topological principles govern their formation remains unclear. The organism-wide molecular and biophysical coordination required to build and maintain these networks during embryonic development has inspired decades of theoretical work, offering predictions about their expected organization. However, the lack of complete three-dimensional (3D) data has limited validation to isolated structures, leaving whole-organism networks unexplored. Here, we developed a computational pipeline for whole-organism 3D imaging to reconstruct the complete vascular and nervous systems of rhesus macaque, mouse, and turtle embryos. Our analysis reveals that both networks share structural principles, including binary branching and scale-invariant bifurcation geometry, maintained across species and throughout development. Yet, from these shared rules emerge fundamentally different architectures. Vasculature exhibits fractal topology with a fractal dimension [~]3, forming space-filling trees that prioritize proximity to every cell in the body. Nervous system networks exhibit a fractal dimension [~]2, forming sheet-like arbors that prioritize electrical signal transmission. This architectural divergence originates from distinct biophysical constraints operating in bifurcations, where vascular junctions minimize energy expenditure while conserving fluid flow and nerve junctions maximize conduction velocity while conserving electrical current. These local optimization rules, iterated across generations, construct organism-wide networks governed by distinct physical constraints, revealing how evolution generated different solutions for fluid versus electrical transport.

developmental biology↗

bioRxiv2026

Soft tissue morphology of the vomeronasal organ in Lontra canadensis and its osteological correlate: Implications for the evolution of the caniform accessory olfactory system

The olfactory system plays a critical role in mammalian environmental perception, with some clades relying on an expanded accessory olfactory (vomeronasal) system (VNS) to detect larger, non-volatile odorants. Mammals make extensive use of this system for social communication between conspecifics. Recent studies have begun to investigate how the VNS changes in response to or as part of ecological transitions. Several studies have identified trends of VNS-associated gene loss or regression in secondarily aquatic mammals. However, continuing discussion on genotype-phenotype correlation within the VNS means that greater effort should be made to investigate the morphology of the VNS in species where it remains poorly understood. Here, we use skeletal and soft-tissue data to demonstrate that the vomeronasal groove, an established osteological correlate for the VNO in bats and primates, is also a valid indicator for its presence in Caniformia. Additionally, we confirm the presence of the VNO in the secondarily aquatic North American river otter (Lontra canadensis) and compare its morphology with that of two close-related species, the semi-aquatic American mink (Neogale vison) and the terrestrial long-tailed weasel (Neogale frenata). This study expands the valid taxonomic scope of the vomeronasal grooves proxy as an osteological correlate, confirms the presence of the VNO in the previously undescribed system of the North American river otter, and highlights the complexity of the mammalian accessory olfactory system.

evolutionary biology↗

bioRxiv2024

RNA-binding proteins control the G2-M checkpoint of the germinal centre B cell

How germinal centre (GC) B cells undergo rapid cell division while maintaining genome stability is poorly understood. Here, we show that the RNA-binding proteins ZFP36L1 and ZFP36L2 act downstream of antigen-sensing and protect GC B cells from replication stress by controlling a cell cycle-related RNA post-transcriptional regulon. ZFP36L1 and ZFP36L2 safeguard faithful completion of mitosis by restraining the expression of CDK1 and cyclin B1, whilst controlling their activity through regulation of a p21-mediated negative feedback loop. In the absence of ZFP36L1 and ZFP36L2, GC B cells arrest in G2-M and die by apoptosis, resulting in curtailed GC responses. This is associated with stalling of the DNA replication fork at active replication initiation zones, which causes replication stress and increased activity of the ATR/CHK1 DNA damage response. Our findings reveal that gene regulation by RNA-binding proteins is essential for a functional G2-M checkpoint to operate in GC B cells.

immunology↗

bioRxiv2024

Remote automated delivery of mechanical stimuli coupled to brain recordings in behaving mice

The canonical framework for testing pain and mechanical sensitivity in rodents is manual delivery of stimuli to the paw. However, this approach is time consuming, produces variability in results, requires significant training, and is ergonomically unfavorable to the experimenter. To circumvent limitations in manual delivery of stimuli, we have created a device called the ARM (Automated Reproducible Mechano-stimulator). Built using a series of linear stages, cameras, and stimulus holders, the ARM is more accurate at hitting the desired target, delivers stimuli faster, and decreases variability in delivery of von Frey hair filaments. We demonstrate that the ARM can be combined with traditional measurements of pain behavior and automated machine-learning based pipelines. Importantly, the ARM enables remote testing of mice with experimenters outside the testing room. Using remote testing, we found that mice habituated more quickly when an experimenter was not present and experimenter presence leads to significant sex-dependent differences in paw withdrawal and pain associated behaviors. Lastly, to demonstrate the utility of the ARM for neural circuit dissection of pain mechanisms, we combined the ARM with cellular-resolved microendoscopy in the amygdala, linking stimulus, behavior, and brain activity of amygdala neurons that encode negative pain states. Taken together, the ARM improves speed, accuracy, and robustness of mechanical pain assays and can be combined with automated pain detection systems and brain recordings to map central control of pain.

neuroscience↗

bioRxiv2024

Behavioral fingerprinting of the naked mole-rat uncovers signatures of eusociality and social touch

The East African naked mole-rat (Heterocephalus glaber) lives in cooperative subterranean colonies and displays a capacity to recognize social novelty, rank, and identity. The sensory cues used for social recognition remain poorly understood, especially because many of their senses are either lost or greatly reduced in comparison to other mammals. Here, we found that naked mole-rats actively touch faces 100% of the time they encounter one another in a tunnel test, followed by milliseconds speed determination of the rank of the other animal. Even in an open arena, naked mole-rats engage in face-to-face touch hundreds of times in a 10-minute social pairing and colonies do so tens of thousands of times over a 24-hour period in their home environment. To demonstrate the prominence of face touch at a molecular level, we show that social housing conditions lead to widespread activation of mechanosensory ion channels, including Piezo2, in neurons that innervate the face, but not the body. Lastly, to determine the ethological relevance of face touch, we reduced its capacity with facial whisker trimming and revealed an apparent inability for animals to recognize colony members. Together, these findings uncover face touch as a prominent social behavior in naked mole-rats that is intimately linked to social recognition.

neuroscience↗

bioRxiv2022

Postpartum estrogen withdrawal induces deficits in affective behaviors and increases ΔFosB in D1 and D2 neurons in the nucleus accumbens core in mice

In placental mammals, estradiol levels are chronically elevated during pregnancy, but quickly drop to prepartum levels following birth. This may produce an "estrogen withdrawal" state that has been linked to changes in affective states in humans and rodents during the postpartum period. The neural mechanisms underlying these affective changes, however, are understudied. We used a hormone-simulated pseudopregnancy (HSP), a model of postpartum estrogen withdrawal, in adult female C57BL/6 mice to test the impact of postpartum estrogen withdrawal on several behavioral measures of anxiety and motivation. We found that estrogen withdrawal following HSP increased anxiety-like behavior in the elevated plus maze, but not in the open field or marble burying tests. Although hormone treatment during HSP consistently increased sucrose consumption, sucrose preference was generally not impacted by hormone treatment or subsequent estrogen withdrawal. In the social motivation test, estrogen withdrawal decreased the amount of time spent in proximity to a social stimulus animal. These behavioral changes were accompanied by changes in the expression of {Delta}FosB, a transcription factor correlated with stable long-term plasticity, in the nucleus accumbens (NAc). Specifically, estrogen-withdrawn females had higher {Delta}FosB expression in the nucleus accumbens core. Using transgenic reporter mice, we found that this increase in {Delta}FosB occurred in both D1- and D2-expressing cells in the NAc core. Together, these results suggest that postpartum estrogen withdrawal impacts anxiety and motivation and increases {Delta}FosB in the NAc core.

neuroscience↗

bioRxiv2021

Identification of touch neurons underlying dopaminergic pleasurable touch and sexual receptivity

Pleasurable touch during social behavior is the key to building familial bonds and meaningful connections. One form of social touch occurs during sexual encounters. Although sexual behavior is initiated in part by touch, and touch is ongoing throughout copulation, the identity and role of sensory neurons that transduce sexual touch remain unknown. A population of sensory neurons labeled by the G-protein coupled receptor Mrgprb4 detect stroking touch in mice, however, these neurons have never been implicated in any natural social behaviors. Here, we study the social relevance of Mrgprb4-lineage neurons by genetically engineering mice to allow activation or ablation of this population and reveal that these neurons are required for sexual receptivity and sufficient to induce dopamine release in the brain. Even in social isolation, optogenetic stimulation of Mrgprb4-lineage neurons through the back skin is sufficient to induce a conditioned place preference and a striking dorsiflexion resembling the lordotic copulatory posture in females. In the absence of Mrgprb4-lineage neurons, female mice no longer find male mounts rewarding: sexual receptivity is supplanted by aggression and a coincident decline in dopaminergic release in the mesolimbic reward pathway. In addition to sexual behavior, Mrgprb4-lineage neurons are also required for social postures induced by female-to-female back touch. Together, these findings establish that Mrgprb4-lineage neurons are the first neurons of a skin-to-brain circuit encoding the rewarding quality of social touch.

neuroscience↗

bioRxiv2021

Behavioral and nociceptor states of inflammatory painacross timescales in 2D and 3D

Ongoing pain is often driven by direct activation of pain-sensing neurons and neuroimmune mediated sensitization. These heightened states of pain alter physiology, reduce motor function, and alter motivation to engage in normal behaviors. The complexity of the pain state has evaded a comprehensive definition, especially in nonverbal animals. Here in mice, we capture the physiological state of sensitized pain neurons at different time points post-inflammation and used computational tools to automatically map behavioral signatures of evoked and spontaneous displays of pain. First, retrograde labeling coupled with electrophysiology of neurons innervating the site of localized inflammation defined critical time points of pain sensitization. Next, we used high-speed videography combined with supervised and unsupervised machine learning tools and uncovered sensory-evoked defensive coping postures to pain. Using 3D pose analytics inspired by natural language processing, we identify movement sequences that correspond to robust representations of ongoing pain states. Surprisingly, with this analytical framework, we find that a commonly used anti-inflammatory painkiller does not return an animals behavior back to a pre-injury state. Together, these findings reveal the previously unidentified signatures of pain and analgesia at timescales when inflammation induces heightened pain states.

neuroscience↗

bioRxiv2021

Inhibition of MRN activity by a telomere protein motif

The MRN complex (MRX in Saccharomyces cerevisiae) initiates the repair of DNA double-stranded breaks (DSBs) and activates the Tel1/ATM kinase, which orchestrates the DNA damage response (DDR). Telomeres prevent DDR activation at chromosome ends, partly by keeping MRN-ATM in check. We show that the multiple activities of the MRX complex are disabled by telomeric protein Rif2 through the action of a short motif (MIN, MRN/X-inhibitory motif) at the N-terminal end of the protein. MIN executes telomeric suppression of Tel1, DDR and and non-homologous end joining (NHEJ) via direct biding to the N-terminal region of Rad50. A combination of biochemical and genetic data suggests that Rif2 promotes a transition within the MRX complex that is not conductive for endonuclease activity, DNA-end tethering or Tel1 kinase activation. We suggests that the MIN motif operates in the RIF2 paralog ORC4 (Origin Recognition Complex 4) in K. lactis and in telomeric protein Taz1 in Schizoccharomyces pombe, which is not evolutionarily related to Orc4/Rif2. These results highlight a potential Achilles heel in Rad50, the regulatory subunit of MRN, which we suggest has been targeted by different telomeric factors in multiple fungal lineages, raising the possibility that analogous approaches might be deployed in other Eukaryotes as well.

genetics↗

bioRxiv2021

Chronic paternal morphine exposure increases sensitivity to morphine-derived antinociception

Parental exposure to drugs of abuse such as opioids can have profound and long-lasting effects on reward processing and drug sensitivity across generations. However, little is known about the impact of long-term paternal exposure to morphine on offspring sensitivity to morphine-derived antinociception during painful experiences. To address this question, we constructed a rat pain scale at millisecond timescales to measure mechanical nociception in a multigenerational morphine exposure paradigm. Surprisingly, while developing the pain scale, we found that von Frey hair filaments (VFHs), the most common stimuli used in pain research, are not painful to rats and morphine did not change the touch-like responses elicited by VFHs. We next deployed this novel pain scale to determine whether chronic morphine exposure in sires impacted pain sensitivity in the next generation. Offspring produced from a cross of morphine-treated sires and drug-naive dams, did not show any baseline changes in sensitivity to mechanical nociception. However, morphine-sired male progeny displayed a higher sensitivity to the antinociceptive properties of morphine, as measured by our pain scale. These findings demonstrate that long-term paternal exposure to morphine increases sensitivity to morphine-derived analgesia in the subsequent generation.

neuroscience↗

bioRxiv2020

A machine-vision approach for automated pain measurement at millisecond timescales

Objective and automatic measurement of pain in mice remains a barrier for discovery in both basic and translational neuroscience. Here we capture rapid paw kinematics during pain behavior in mice with high-speed videography and automated paw tracking with machine and deep learning approaches. Our statistical software platform, PAWS (Pain Assessment at Withdrawal Speeds), uses a univariate projection of paw position over time to automatically quantify fast paw dynamics at the onset of paw withdrawal and also lingering pain-related behaviors such as paw guarding and shaking. Applied to innocuous and noxious stimuli across six inbred mouse strains, a linear discriminant analysis reveals a two-dimensional subspace that separates painful from non-painful stimuli on one axis, and further distinguishes the severity of pain on the second axis. Automated paw tracking combined with PAWS reveals behaviorally-divergent mouse strains that display hypo- and hyper-sensitivity to mechanical stimuli. To demonstrate the efficacy of PAWS for detecting hypersensitivity to noxious stimuli, we chemogenetically activated pain-aversion neurons in the amygdala, which further separated the behavioral representation of pain-related behaviors along a low-dimensional path. Taken together, this automated pain quantification approach should increase the ease and objectivity of collecting rigorous behavioral data, and it is compatible with other neural circuit dissection tools for determining the mouse pain state.

neuroscience↗

bioRxiv2019

Evoked and spontaneous pain assessment during tooth pulp injury

Injury of the tooth pulp is excruciatingly painful and yet the receptors and neural circuit mechanisms that transmit this form of pain remain poorly defined in both the clinic and preclinical rodent models. Easily quantifiable behavioral assessment in the rodent orofacial area remains a major bottleneck in uncovering molecular mechanisms that govern inflammatory pain in the tooth. Here we use a dental pulp injury model in the mouse and expose the tooth pulp to the outside environment, a procedure we have previously shown produces pulpal inflammation. We demonstrate here with RNAscope technology in the trigeminal ganglion of injured mice, an upregulation of genes that contribute to the inflammatory pain state. Using both evoked and spontaneous measures of pain in the orofacial area, including application of von Frey Hair filaments and pain feature detection with the mouse grimace scale, we reveal a differential timeline of induction of spontaneous pain versus mechanical allodynia following pulpal injury. This work demonstrates that tooth pain can be easily assessed in freely behaving mice using approaches common for other types of pain assessment. Harnessing these assays in the orofacial area during gene manipulation should assist in uncovering mechanisms for tooth pulp inflammation and other forms of trigeminal pain.

neuroscience↗