Biology subjects

Szymanska, K.

Publications and source records attributed to Szymanska, K..

6 recordsLinked to original sources

bioRxiv2026

Chronoecological interactions: Temporal niche-switching by black-striped mice after agonistic food competition with a dominant sympatric mouse species

When novel nutrient-rich food sources become available to species sharing the same natural habitat, interspecies competition may arise, yielding insights into the ecological and social dynamics of the observed species. Here, we investigated food consumption patterns, and consequent social interactions, by two sympatric species of mice in response to a novel nutrient-rich food source. By deploying, in the mices natural habitat, baited video-monitored chambers, we collected, over a 5-month period, 1805 observations of food visiting by Apodemus agrarius and Apodemus flavicollis. We also documented interspecific encounters, with 86.7% of the cases showing agonism. In these interspecies agonistic encounters, A. flavicollis was always the initiator of agonism, attacking within 2 sec in 92.3% of the cases, and being dominant over A. agrarius in 84.6%. Analysis of food visiting behavior revealed that, initially, both species preferred nocturnality. However, after the interspecies fights, A. agrarius switched its temporal preference to diurnality, leading to temporal niche segregation between the two species and a significant reduction of interspecies encounters. Moreover, A. agrarius demonstrated hour-specific avoidance of A. flavicollis, visiting significantly less in hours with A. flavicollis compared to hours without. Through temporal niche switching, A. agrarius managed to access the food source safely, without fights. In contrast, A. flavicollis remained consistently nocturnal across the entire study. Notably, our study presents the first 24h foraging actogram for free-living rodents. Moreover, while rodent interspecific competition is a well-known phenomenon, most of what we know about it comes from indirect observations. Direct observations of rodent interspecific interactions in nature are rare. Our work is the first direct (video-monitored) observation of temporal switch-inducing interspecies interactions in nature. As free-living rodents are currently considered a major model system for the study of interspecific competition, these results may offer precious insights for a better understanding of social dynamics, especially in asymmetric relationships. Furthermore, our findings highlight the significance of considering temporal dynamics in studies of interspecific interactions.

animal behavior and cognition↗

bioRxiv2025

Nonsense, but not frameshift, truncating mutations result in Cyclin D2 stabilisation in an induced pluripotent stem cell model of MPPH

Stabilisation of Cyclin D2 is the underlying cause of a range of neurodevelopmental disorders, characterised by megalencephaly, cortical migration defects and overgrowth. Intracellular CCND2 is vital for mTOR pathway signalling, with inhibition of mTOR resulting in CCND2 phosphorylation and degradation by the ubiquitin proteasome system. Mutations at the regulatory c-terminus of CCND2, and in proteins that regulate mTOR such as PTEN, PIK3CA, AKT3 and TSC1/2, result in CCND2-stabilisation and overgrowth. To determine the molecular and cellular mechanisms underpinning the neurodevelopmental defects observed in Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus (MPPH) syndrome, we generated human induced pluripotent stem cell (iPSC) derived models of CCND2-associated disease. Using CRISPR-Cas9 we generated lines containing either a pathogenic CCND2 variant (c.814G>T, p.Glu272Ter) or frameshift variants in the final exon of CCND2, all of which truncate CCND2 before the critical Thr-280 residue, required for its phosphorylation and degradation. We observed truncating frameshift variants do not result in CCND2 stabilization, whereas the single nucleotide c.814G>T, p.Glu272Ter substitution does, mimicking the effect seen in MPPH patients. Differentiation into human cortical spheroids (hCS) revealed all CCND2-truncating lines continued to express PAX6 beyond the neural progenitor (NP) expansion phase. Furthermore, both the homozygous and heterozygous p.Glu272Ter hCS failed to produce mature Tbr-1 expressing neurons, while some expression was observed in the frameshift hCS, highlighting differences in neurogenesis between frameshift and nonsense lines. Despite all lines truncating CCND2 and removing Thr-280, our data implies that frameshift truncations do not stabilise CCND2. In comparison, truncation of CCND2 through introduction of a single nucleotide nonsense variant results in CCND2 stabilisation, mimicking MPPH.

developmental biology↗

bioRxiv2025

The RNA splicing factor PRPF8 is required for left-right organiser cilia function and determination of cardiac left-right asymmetry via regulation of Arl13b splicing

Cilia function in the left-right organizer (LRO) is critical for determining internal organ asymmetry in vertebrates. To further understand the genetics of left-right asymmetry, we isolated a mouse mutant with laterality defects, l11Jus27, from a random mutagenesis screen. l11Jus27 mutants carry a missense mutation in the pre-mRNA processing factor, Prpf8. cephaloph[o]nus (cph) mutant zebrafish, carrying a protein truncating mutation in prpf8, phenocopy the laterality defects of l11Jus27 mutants. Prpf8 mutant mouse and fish embryos have increased expression of an alternative transcript encoding the cilium-associated protein, ARL13B, that lacks exon 9. In zebrafish, over-expression of the arl13b transcript lacking exon 9 perturbed cilium formation and caused laterality defects. The shorter ARL13B protein isoform lacked interactions with intraflagellar transport proteins. Our data suggest that PRPF8 plays a prominent role in LRO cilia by through the regulation of alternative splicing of ARL13B, thus uncovering a new mechanism for cilia-linked developmental defects.

developmental biology↗

bioRxiv2020

Regulation of canonical Wnt signalling by ciliary protein MKS1 and Ubiquitin Proteasome System component UBE2E1.

A functional primary cilium is essential for normal and regulated signalling. Primary ciliary defects cause a group of developmental conditions known as ciliopathies, but the precise mechanisms of signal regulation by the cilium remain unclear. Previous studies have implicated the ubiquitin proteasome system (UPS) in regulation of Wnt signalling at the ciliary basal body. Here, we provide mechanistic insight into ciliary ubiquitin processing in cells and for a ciliopathy mouse model lacking the ciliary protein Mks1. In vivo loss of Mks1 sensitizes cells to proteasomal disruption, leading to abnormal accumulation of ubiquitinated proteins. To substantiate a direct link between MKS1 and the UPS, we identified UBE2E1, an E2 ubiquitin-conjugating enzyme that polyubiquitinates {beta}-catenin, and RNF34, an E3 ligase, as novel interactants of MKS1. UBE2E1 and MKS1 colocalized, particularly during conditions of ciliary resorption, and loss of UBE2E1 recapitulates the ciliary and Wnt signalling phenotypes observed during loss of MKS1. Levels of UBE2E1 and MKS1 are co-dependent and UBE2E1 mediates both regulatory and degradative ubiquitination of MKS1. Furthermore, we demonstrate that processing of phosphorylated {beta}-catenin occurs at the ciliary base through the functional interaction between UBE2E1 and MKS1. These observations suggest that correct {beta}-catenin levels are tightly regulated at the primary cilium by a ciliary-specific E2 (UBE2E1) and a regulatory substrate-adaptor (MKS1), confirming the fundamental role of UPS defects in the molecular pathogenesis of ciliopathies.

molecular biology↗

bioRxiv2017

Human iPSC-derived RPE and retinal organoids reveal impaired alternative splicing of genes involved in pre-mRNA splicing in PRPF31 autosomal dominant retinitis pigmentosa

Mutations in pre-mRNA processing factors (PRPFs) cause 40% of autosomal dominant retinitis pigmentosa (RP), but it is unclear why mutations in ubiquitously expressed PRPFs cause retinal disease. To understand the molecular basis of this phenotype, we have generated RP type 11 (PRPF31-mutated) patient-specific retinal organoids and retinal pigment epithelium (RPE) from induced pluripotent stem cells (iPSC). Impaired alternative splicing of genes encoding pre-mRNA splicing proteins occurred in patient-specific retinal cells and Prpf31+/- mouse retinae, but not fibroblasts and iPSCs, providing mechanistic insights into retinal-specific phenotypes of PRPFs. RPE was the most affected, characterised by loss of apical-basal polarity, reduced trans-epithelial resistance, phagocytic capacity, microvilli, and cilia length and incidence. Disrupted cilia morphology was observed in patient-derived-photoreceptors that displayed progressive features associated with degeneration and cell stress. In situ gene-editing of a pathogenic mutation rescued key structural and functional phenotypes in RPE and photoreceptors, providing proof-of-concept for future therapeutic strategies.\n\neTOCPRPF31 is a ubiquitously expressed pre-mRNA processing factor that when mutated causes autosomal dominant RP. Using a patient-specific iPSC approach, Buskin and Zhu et al. show that retinal-specific defects result from altered splicing of genes involved in the splicing process itself, leading to impaired splicing, loss of RPE polarity and diminished phagocytic ability as well as reduced cilia incidence and length in both photoreceptors and RPE.\n\nHighlightsO_LISuccessful generation of iPSC-derived RPE and photoreceptors from four RP type 11 patients\nC_LIO_LIRPE cells express the mutant PRPF31 protein and show the lowest expression of wildtype protein\nC_LIO_LIPRPF31 mutations result in altered splicing of genes involved in pre-mRNA splicing in RPE and retinal organoids\nC_LIO_LIPrpf31 haploinsufficiency results in altered splicing of genes involved in pre-mRNA splicing in mouse retina\nC_LIO_LIRPE cells display loss of polarity, reduced barrier function and phagocytosis\nC_LIO_LIPhotoreceptors display shorter and fewer cilia and degenerative features\nC_LIO_LIRPE cells display most abnormalities suggesting they might be the primary site of pathogenesis\nC_LIO_LIIn situ gene editing corrects the mutation and rescues key phenotypes\nC_LI

genetics↗

bioRxiv2017

CiliaCarta: An Integrated And Validated Compendium Of Ciliary Genes

The cilium is an essential organelle at the surface of most mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We found experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins. In addition, we show that OSCP1, which has previously been implicated in two distinct non-ciliary functions, causes a cilium dysfunction phenotype when depleted in zebrafish. The candidate list forms the basis of CiliaCarta, a comprehensive ciliary compendium covering 836 genes. The resource can be used to objectively prioritize candidate genes in whole exome or genome sequencing of ciliopathy patients and can be accessed at http://bioinformatics.bio.uu.nl/john/syscilia/ciliacarta/.

bioinformatics↗