Biology subjects

Rayfield, E. J.

Publications and source records attributed to Rayfield, E. J..

3 recordsLinked to original sources

bioRxiv2026

Loss of lmx1ba drives premature osteoarthritis through disruption of skeletal homeostasis

Osteoarthritis is increasingly recognised as a disease of failed integration across the whole joint unit; however, the mechanisms that co-ordinate tissue integrity from development through to adult homeostasis remain largely unresolved. The LIM-homeodomain transcription factor LMX1B is a key determinant of embryonic skeletal patterning, but how it functions to regulate skeletal integrity in the mature skeleton is unknown. Recently, LMX1B was identified as a key driver of osteoarthritis. Here we show that loss of lmx1ba in zebrafish causes premature and progressive severe osteoarthritic pathology in adult spines and jaws, despite largely normal early skeletal patterning, revealing a conserved and continuous requirement for lmx1ba in joint maintenance beyond development. At a cellular level, loss of lmx1ba decouples osteoblast and osteoclast-mediated remodelling leading to bone overgrowth, heterogeneity of bone properties causing increased incidence of spontaneous fractures, and progressive abnormalities in spine morphology. In parallel, we observe degeneration of the intervertebral disc and dysregulation of the proteome and glycosaminoglycans indicative of disrupted extracellular matrix and a breakdown of the coordinated regulation of hard and soft tissue interfaces, which at the organismal level leads to altered joint performance. Notably, degeneration is restricted to mobile joints, and is not observed in cranial sutures, demonstrating a selective requirement for lmx1ba in mechanically active tissues. These changes are consistent with a model of spatially disrupted matrix properties that, under cyclic loading, promote progressive tissue damage. Our findings support a model in which continued expression of LMX1B in adulthood is required to maintain joint structures throughout life.

physiology↗

bioRxiv2025

Theoretical Morphology of Avian Wing Planform Reveals Variable Optimisation to Flight Style

Bird wings exhibit a broad degree of functional and shape variation, though the exact nature of the form-function relationship is uncertain. Recent analysis suggests that functional variability is explained by linear non-shape-based traits and that shape variation is largely explained by phylogeny. We assay the relationship between wing planform shape and functional performance using a theoretical morphospace approach that eschews assumptions of the functional optimality of empirical morphologies. Empirical properties are considered post hoc relative to their positions in the functional performance landscapes. We produce a theoretical morphospace of wing planform shapes and compare the functional performance and optimality of theoretical shapes with 1139 extant taxa. These tests cover flight metrics and combinations linked with 7 flight niches. Metrics pertaining to agile flight strongly constrain shape, with hovering, diving and hawking birds developing optimal planforms. Marine soarers are suboptimal for metrics linked with efficient and manoeuvrable flight. Many taxa, principally passerines, remain suboptimal for all studied metrics and combinations. This suggests flight performance constrains planforms unevenly across birds. Phylomorphospace analysis suggests planform shape is only weakly influenced by phylogeny and functional optimality correlates closely with flight styles. This suggests wing shape remains a determining factor in how birds fly.

paleontology↗

bioRxiv2017

A zebrafish model of developmental joint dysplasia: Manipulating the larval mechanical environment to drive the malformation and recovery of joint shape

Developmental dysplasia of the hip (DDH), a malformation of the acetabulum, is a frequent cause of early onset osteoarthritis. The disease encompasses a spectrum of severities, some of which are more amenable to treatment. Embryonic immobilisation significantly impairs the development of joint shape however the impact of this malformation to the function and growth of the joint in the short to medium term is unclear. We developed a novel model of developmental joint dysplasia using the zebrafish jaw joint to identify the mechanisms regulating cellular plasticity and ability to recover joint shape and function. Larval zebrafish were immobilised either pharmacologically or using targeted ablation of jaw muscles to induce an altered joint shape. Following restoration of muscle activity we dynamically monitored the joint shape and function in individuals at cellular resolution impossible in other vertebrate species. Reflecting the variability of the human condition we found a proportion of joints will recover both their shape and function, while others will not; despite coming from a genetically homogenous population. This allowed us to study what controls likelihood of recovery; we identified a number of cellular changes that predict likelihood of functional recovery, including position of precursor cells, and specific patterns of proliferation, migration and differentiation in joints and associated connective tissues. These factors together predict recovery better than severity of malformation alone. Using Finite Element Analysis we studied the mechanics of joints representative of ones that recover and those that fail to identify differences in patterns of strain that could explain the cellular behaviours that underpin likelihood of recovery. Thus, this model would enable the study of the short to long term impact of altered joint shape on function and could help to identify the changes that render an individual more receptive to treatment and therefore may potentially be indicative of long term joint health.

developmental biology↗