Biology subjects

Warner, S. E.

Publications and source records attributed to Warner, S. E..

3 recordsLinked to original sources

bioRxiv2026

Ephrin Signaling Patterns Sensory Neurons During Tissue Homeostasis in Planarians

Eph and ephrin genes encode receptor-ligand pairs that mediate contact-dependent cell signaling and are essential for nervous system development. However, less is known about the role of Ephrin signaling during adult tissue homeostasis and regeneration. Here, we investigated the role of Ephrin signaling in neural patterning in the planarian Schmidtea mediterranea. We discovered that RNAi against the Eph receptor EphR1 led to striking ectopic expression of the mechanosensory neuron markers pkd1L-2 and hmcn-1-L, without obvious disruption of the overall architecture of the central nervous system. To investigate the basis of this phenotype, we identified additional Eph receptor homologs and four putative ephrin ligands and assessed their function. An RNAi screen revealed that ephrin-1 phenocopies the defects of EphR1 RNAi. Temporal analyses of EphR1 and ephrin-1 inhibition revealed a progressive increase in pkd1L-2+ and hmcn-1-L+ cells, indicating an unappreciated role for Ephrin signaling in regulating neural patterning and cell number during adult tissue homeostasis. Together, these findings provide a framework for dissecting Ephrin-dependent mechanisms in adult tissue maintenance and regeneration.

developmental biology↗

bioRxiv2025

Soft tissue constraints on joint mobility in the avian shoulder

Joints and their surrounding soft tissues facilitate and restrict vertebrate skeletal motion. Measures of maximal joint mobility provide insight into articular function and its limits on potential joint motion and thereby behaviour. In extinct vertebrates the reconstruction of joint mobility permits us to decipher shifts in locomotor evolution. Such measurements are generally limited to studies of osteological joint mobility. However, only a subset of osteologically feasible poses are biologically feasible because true joint mobility is limited by soft tissues, such as ligaments, that seldomly preserve in the fossil record. To address this issue, we implemented an in silico model to simulate avian glenohumeral (shoulder) movement and the constraints imposed by six ligaments on its joint mobility. We evaluated our in silico model of the partridge shoulder joint with measured ex vivo shoulder mobility using X-ray Reconstruction of Moving Morphology (XROMM). Our results indicate that modelling ligamentous constraints is integral to accurately quantifying shoulder function due to the role of ligaments in maintaining articular contact during complex glenohumeral motion. Our approach enables more confident estimates of functional joint mobility in both extant and extinct vertebrates and thereby stands to improve inferences of behaviour and musculoskeletal function in the vertebrate fossil record.

evolutionary biology↗

bioRxiv2019

Chronic infection of adult zebrafish with rough or smooth variant Mycobacterium abscessus causes necrotising inflammation and differential activation of host immunity

Infections caused by Mycobacterium abscessus are increasing in prevalence within patient groups with respiratory comorbidities. Initial colonisation by the smooth colony M. abscessus (S) can be followed by an irreversible genetic switch into a highly inflammatory rough colony M. abscessus (R), often associated with a decline in pulmonary function. Our understanding of the role of adaptive immunity in M. abscessus pathogenesis is largely unknown. Here, we have used intraperitoneal infection of adult zebrafish to model M. abscessus pathogenesis in the context of fully functioning host immunity. We find infection with the R variant penetrates host organs causing an inflammatory immune response leading to necrotic granuloma formation within 2 weeks. The R bacilli are targeted by T cell-mediated immunity and burden is constrained. Strikingly, the S variant colonises host internal surfaces at high loads and is met with a robust innate immune response but little T cell-mediated immunity. Invasive granuloma formation is delayed in S variant infection compared to R variant infection upon which T cell-mediated immunity is required to control infection. In mixed infections, the S variant outcompetes the R variant. We also find the R variant activates host immunity to the detriment of S variant M. abscessus in mixed infections. These findings demonstrate the applicability of the adult zebrafish to model persistent M. abscessus infection and provide insight into the immunopathogenesis of chronic M. abscessus infection.

microbiology↗