bioRxiv Science⌕ Search

Biology subjects

Begall, S.

Publications and source records attributed to Begall, S..

12 recordsLinked to original sources

Absence of the Earths magnetic field activates stress-related brain circuits in a mammal

The Earths magnetic field is a constantly available cue for animals with a magnetic sense. While magnetic navigation is best studied in migratory birds, a magnetic sense is also found in some mammals. Among these, it is most thoroughly studied in African mole-rats of the genus Fukomys, subterranean mammals that navigate in kilometre-long dark tunnel systems. Our understanding of the neural pathways involved in magnetoreception remains incomplete. To address this, we here performed an unbiased whole-brain screen for magnetically induced neuronal activity in the mole-rat brain. We set up MoBI-DisC (Mole-rat Brain Imaging with iDISCO and ClearMap), an experimental pipeline that combines global c-Fos immunolabelling, tissue clearing, light-sheet microscopy, and mapping to a novel 3D brain atlas. To identify brain areas involved in magnetosensation, we exposed mole-rats to a changing magnetic field and compared their brain activity to that of control animals exposed to a near-zero magnetic field. Unexpectedly, we found that the near-zero magnetic field exposure activated many brain areas, predominantly those involved in stress and anxiety responses. These included the amygdala, the bed nucleus of the stria terminalis, the substantia innominata, and the periaqueductal grey. This suggests that magnetic field deprivation acts as a physiological stressor in mole-rats. To test this, we conducted a place-preference test and found that mole-rats avoid entering a zone with a near-zero magnetic field, consistent with the hypothesis that this condition is not neutral for these animals. In summary, we present a novel pipeline for unbiased mapping of neural activity in subterranean mole-rats and uncover evidence of stress and avoidance responses to the absence of an Earth-strength magnetic field.

neuroscience↗

Multimodal imaging reveals no evidence for magnetite-based magnetoreceptors in the mole-rat eye

Magnetoreception, the ability to perceive the geomagnetic field, is widespread across animals. The underlying sensory mechanism remains elusive, but a long-standing hypothesis proposes single-domain magnetite linked to mechanosensitive ion channels. The Ansells mole-rat (Fukomys anselli) is a subterranean rodent with a magnetic sense, and published behavioral and histological data are consistent with magnetite-based magnetoreceptors in the cornea or retina. Here, we systematically screened for magnetite in the mole-rat eye, combining iron detection via enhanced Prussian blue staining and synchrotron X-ray fluorescence microscopy (XFM) with magnetic detection via MRI quantitative susceptibility mapping (MRI-QSM) and quantum-diamond microscopy (QDM). This revealed only a few iron particles in the retina and cornea, which predominantly overlapped with titanium or chromium, indicating a non-biogenic origin. XFM showed iron-enriched lines in the cornea, but these did not show ferrimagnetic signals. Focusing on other ocular tissues, MRI-QSM revealed the highest susceptibility in the ciliary body, where iron-rich pigmented cells were identified. A TEM-screen, however, failed to detect single-domain magnetite particles in these cells. We conclude that our high-sensitivity multimodal screen provides no evidence for magnetite-based magnetoreceptors in the mole-rat eye, suggesting that mole-rat magnetoreceptors either do not reside in the eye or are based on different physical principles.

neuroscience↗

Hyaluronan and skin elasticity: Are subterranean mammals special?

It has been hypothesized that subterranean mammals have evolved increased skin elasticity to reduce friction when moving through their underground tunnel systems. This trait is commonly believed to be mediated by greatly elongated hyaluronan (HA) polymers in the dermal extracellular matrix, which have been reported from different distantly related burrowing mammals. However, replicating these findings has proven difficult, and a mechanism by which HA polymer size could modify skin elasticity has not been proposed. In fact, experimental data on skin biomechanics in burrowing mammals are currently unavailable. Here, we quantify the molecular mass of HA polymers extracted from the tissues of Ansells mole-rat (Fukomys anselli), a burrowing rodent yet unstudied in that respect, and investigate skin biomechanics in subterranean and epigeic (aboveground foraging) small mammal species by means of in vivo-cutometry. We did not recover abundant extremely elongated HA polymers in Ansells mole-rat, conflicting with published findings in congeneric species and the naked mole-rat. Polymer length was found to be increased compared to guinea pigs across tissues, though. Our data on skin biomechanics indicate that subterranean mammal skin is not consistently more elastic than that of epigeic forms. Interestingly, the skin of the naked mole-rat was characterized by very high stiffness. Uniaxial tensile tests demonstrated that it also exhibits exceptional tensile strength. Hence, we challenge the idea that hyaluronan or a subterranean ecology notably influences skin elasticity in small mammals and suggest that previous studies may have confused elasticity with skin looseness, which constitutes a different phenomenon.

zoology↗

Neuronal recordings in head-fixed and freely-moving mole-rats

Mole-rats are subterranean rodents that have evolved remarkable sensory adaptations to life in underground tunnel systems, yet their neural mechanisms remain largely unexplored. Here, we present a protocol for in vivo electrophysiological recordings in awake, head-fixed, and freely moving African mole-rats (Fukomys anselli/micklemi), overcoming unique challenges of studying the neurobiology of subterranean species. For example, we find that mole-rat brain physiology impacts survival after surgeries, with higher carbon dioxide concentrations required for recovery compared to other rodents, likely due to a mutation in the chloride-potassium symporter KCC2. Having addressed the challenges, we used tetrodes and Neuropixels probes to record single-unit activity and local field potentials (LFP) across several cortical and subcortical regions for several weeks. We observed single units responsive to auditory and visual stimuli in the superior colliculus, and hippocampal recordings in freely moving mole-rats revealed prominent theta rhythms at frequencies lower than those observed in any other rodent species to date. Finally, we performed integrated three-dimensional and two-dimensional probe-track analysis within the same brain using tissue clearing, light sheet imaging, rehydration, and vibratome sectioning, and we present a newly developed stereotaxic brain atlas for implantation and histological alignment. The established methodology will guide future studies in comparative rodent neurobiology, providing further insights into neurobiological adaptations to subterranean environments. Given their phylogenetic and ecological similarities, we expect our protocols to be transferable to other subterranean species, including the widely studied naked mole-rat (Heterocephalus glaber). HighlightsO_LIProtocols for chronic and acute electrode implantations in mole-rats C_LIO_LIStereotaxic brain atlas for the Ansells mole-rat (https://doi.org/10.17617/3.UNDKRO) C_LIO_LINeuropixels and tetrode single-unit recordings in head-fixed and freely moving mole-rats C_LIO_LIIntegrated 3D (tissue clearing) and 2D (histology) probe-track analysis within the same brain C_LIO_LIDiscovery of low-frequency hippocampal theta rhythm in Ansells mole-rats C_LI

neuroscience↗

De novo genome assembly of Ansell's mole-rat (Fukomys anselli)

Ansells mole-rat (Fukomys anselli) is an African rodent known for its subterranean lifestyle and unique phenotypic traits, including extreme longevity, magnetoreception, and a cooperative breeding social structure. Efforts to dissect the genetic architecture of these traits and to decipher their phylogenetic relationships within the broader African mole-rat family would greatly benefit from a reference-grade genome. Here, we report a first genome assembly of a male Ansells mole-rat. By combining Oxford Nanopore Technologies (ONT) long-reads and Illumina short-reads with Hi-C data, we generated a chromosome level assembly with a total length of 2.27 Gb, 412 scaffolds and a scaffold N50 of 72.4 Mb. We identified 99.54% of expected genes and annotated 29,094 transcripts using RNA sequencing data. This high-quality de novo genome of Fukomys anselli lays the foundation for dissecting the genetic and evolutionary basis of its extraordinary traits and resolving African mole-rat phylogeny. ARTICLE SUMMARYBekavac, Coimbra, and Busa et al. assemble a de novo genome of a male Fukomys anselli individual. They use short-read and long-read whole genome sequencing and Hi-C sequencing to achieve chromosome-level contiguity, and annotate the genome using RNA-seq from nine diverse tissues. This high-quality genome enables exploration of the genetic basis of Ansells mole-rats remarkable traits, including longevity, hypoxia tolerance, and magnetoreception. It also allows for comprehensive analysis of the currently-contested phylogenetic relationships within the mole-rat family.

genomics↗

An interactive cellular ecosystem blocks epithelial transformation in naked mole-rat

Long-lived species suppress cancer despite accumulating somatic mutations throughout life, but how this is achieved in renewing tissues remains unclear. Here, we show that naked mole-rat skin uncouples high cellular turnover from cancer risk through coordinated epithelial and stromal mechanisms that constrain clonal outgrowth and suppress tumor-promoting inflammation. Despite elevated epidermal proliferation and mutational burden, naked mole-rat skin maintains tissue integrity through an expanded pool of early committed progenitor (hybrid) cells and replication-coupled genome maintenance pathways. Under chronic carcinogenic stress, undifferentiated basal cells replenish the hybrid progenitor pool. This dilutes initiated clones and permits only limited selective expansion of rare cancer gene-mutant clones. Depletion of the hybrid compartment shifts this protective state toward clonal expansion and inflammatory activation. These expanding clones are further constrained by a highly tumor-suppressive stromal microenvironment, driven by fibroblasts that adopt a metabolically restricted, non-inflammatory program. Together, our data uncover a multi-layered tumor-suppressive strategy that couples turnover-driven regeneration with an anti-permissive stromal niche to prevent malignant progression under mutagenic stress.

cancer biology↗

Scleral appearance is not a correlate of domestication in mammals

Numerous hypotheses try to explain the unusual appearance of the human eye with its bright sclera and transparent conjunctiva and how it could have evolved from a dark-eyed phenotype, as is present in many non-human primates. Recently, it has been argued that pigmentation defects induced by self-domestication may have led to bright-eyed ocular phenotypes in humans and some other primate lineages, such as marmosets. However, it has never been systematically studied whether actual domesticated mammals consistently deviate from wild mammals in regard to their conjunctival pigmentation and if this trait might therefore be part of a domestication syndrome. Here, we test this idea by drawing phylogenetically informed comparisons from a photographic dataset spanning 13 domesticated mammal species and their closest living wild relatives. We did not recover significant differences in scleral appearance or irido-scleral contrast between domesticated and wild forms, suggesting that conjunctival depigmentation, unlike cutaneous pigmentation disorders, is not a general correlate of domestication. Regardless of their domestication status, macroscopically depigmented conjunctivae were observed in carnivorans and lagomorphs, whereas ungulates generally displayed darker eyes. Based on our dataset, we also present preliminary evidence for a general increase of conjunctival pigmentation with eye size in mammals. Our findings suggest that conjunctival depigmentation in humans is not a byproduct of self-domestication, even if we assume that our species has undergone such a process in its recent evolutionary history.

zoology↗

Perioral secretions enable complex social signaling in African mole-rats (genus Fukomys)

Subterranean common mole-rats of the genus Fukomys (family Bathyergidae) live in large cooperatively-breeding families. Odor cues have been hypothesized to importantly mediate social behaviors in the underground ecotope, but only little is known about the role of olfactory signaling in burrowing mammals. Here we characterize the so far neglected perioral glands of Fukomys and other African mole-rats as an important source of olfactory social information. Histology demonstrates these structures to be derived sebaceous glands that are developed regardless of sex and reproductive status. However, gland activity is higher in Fukomys males, leading to sexually dimorphic patterns of stain and clotting of the facial pelage. Behavioral assays revealed that conspecifics prefer male but not female perioral swabs over scent samples from the back fur and that male sebum causes similar attraction as anogenital scent, a known source of social information in Fukomys. Finally, we assessed volatile compounds in the perioral sebum of the giant mole-rat (Fukomys mechowii) via GCxGC-MS-based metabolomic profiling. Volatiles displayed pronounced sex-specific signatures but also allowed to differentiate between intrasexual reproductive status groups. These different lines of evidence suggest that mole-rat perioral glands provide complex odor signals that play a crucial role in social communication.

zoology↗

The evolution and biological correlates of hand preferences in anthropoid primates

The evolution of human right-handedness has been intensively debated for decades. Manual lateralization patterns in non-human primates have the potential to elucidate evolutionary determinants of human handedness. However, restricted species samples and inconsistent methodologies have so far limited comparative phylogenetic studies. By combining original data with published literature reports, we assembled data on hand preferences for standardized object manipulation in 1,786 individuals from 38 species of anthropoid primates, including monkeys, apes, and humans. Based on that, we employ quantitative phylogenetic methods to test prevalent hypotheses on the roles of ecology, brain size and tool use in primate handedness evolution. We confirm that human right-handedness represents an unparalleled extreme among anthropoids and found taxa displaying population-level handedness to be rare. Species-level direction of manual lateralization was largely uniform among non-human primates and did not strongly correlate with any of the selected biological predictors, nor with phylogeny. In contrast, we recovered highly variable patterns of hand preference strength, which show signatures of both ecology and phylogeny. In particular, terrestrial primates tend to display weaker hand preferences than arboreal species. These results challenge popular ideas on primate handedness evolution, especially the postural origins hypothesis. Furthermore, they point to a potential adaptive benefit of disparate lateralization strength in primates, a measure of hand preference that has often been overlooked in the past. Finally, our data show that human lateralization patterns do not align with trends found among other anthropoids, suggesting that unique selective pressures gave rise to the unusual hand preferences of our species.

animal behavior and cognition↗

Ocular pigmentation in humans, great apes, and gibbons is not suggestive of communicative functions - having an eye on the 'cooperative eye hypothesis'

Pigmentation patterns of the visible part of the eyeball, encompassing the iris and portions of the sclera, have been discussed to be linked to social cognition in primates. In the context of the cooperative eye hypothesis, the white sclera of humans has been viewed as a derived adaptive trait, enhancing communication via glance cueing. Here, we provide a comparative analysis of ocular pigmentation patterns in 15 species of hominoids (humans, great apes & gibbons) representing all extant ape genera, based on photographs and literature data. Additionally, we quantify hominoid scleral exposure on the genus level during different glancing situations. Our data reveals a continuum of eye pigmentation traits among the studied taxa. Gibbons display darker, more uniformly colored eyes than great apes and expose less sclera, particularly during averted glancing. Iridoscleral contrasts in orangutans and gorillas approach the human condition but differ between congeneric species. Contrary to recent discussions, we found chimpanzee eyes to exhibit a cryptic coloration scheme that resembles gibbons more than other great apes and that does not enhance glance cueing or gaze following. We critically evaluate the evidence for links between social cognition and eye pigmentation in primates, concluding that the cooperative eye hypothesis cannot convincingly explain the patterns observed. Although the human eye exhibits unique traits that are likely linked to social communication, high iridoscleral contrast is not one of them. Differences in scleral pigmentation between great apes and humans are gradual and might have arisen via genetic drift and sexual selection.

zoology↗

Eyes are essential for magnetoreception in a mammal

Several groups of mammals use the Earths magnetic field for orientation, but their magnetosensory organ remains unknown. The Ansells mole-rat (Fukomys anselli) is a subterranean rodent with innate magnetic orientation behavior. Previous studies proposed that its magnetoreceptors are located in the eye. To test this hypothesis, we assessed magnetic orientation in enucleated mole-rats. Initially, we demonstrate that enucleation of mole-rats does not lead to changes in routine behaviors. We then studied magnetic compass orientation by employing a well-established nest building assay. To ensure that directional responses were based on magnetic parameters, we tested animals under four magnetic field alignments. In line with previous studies, control animals exhibited a significant preference to build nests in magnetic south-east. In contrast, enucleated mole-rats built nests in random magnetic orientations, suggesting an impairment of their magnetic sense. The results provide robust support for the hypothesis that mole-rats perceive magnetic fields with their minute eyes.

animal behavior and cognition↗

Status-dependent aging rates in long-lived, social mole-rats are shaped by HPA stress axis

Sexual activity and/or reproduction doubles life expectancy in the long-lived rodent genus Fukomys. To investigate the molecular mechanisms underlying this phenomenon, we analyzed a total of 636 RNA-seq samples across 15 tissues. This analysis suggests that the differences in life expectancy between reproductive and non-reproductive mole-rats are mainly caused by critical changes in the regulation of the hypothalamic-pituitary-adrenal stress axis, which we further substantiate with a series of independent evidence. In accordance with previous studies, the up-regulation of the proteasome and several so-called "anti-aging molecules", such as DHEA, is also linked with enhanced life expectancy. On the other hand, several our results oppose crucial findings in short-lived model organisms. For example, we found the up-regulation of the IGF1/GH axis and several other anabolic processes to be compatible with a considerable lifespan prolongation. These contradictions question the extent to which findings from short-lived species can be transferred to longer-lived ones.

genomics↗