Company of Biologists

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder characterised by loss of dopaminergic neurons from the substantia nigra pars compacta, a region of the human brain involved in motor control. PD can be familial (arising from inherited genetic mutation) or sporadic (resulting from a multifactorial combination of ageing, environmental exposures and genetic susceptibility). Neuronal function depends on mitochondrial energy production to maintain membrane potential and neurotransmission, but these processes can cause mitochondrial damage through the generation of reactive oxygen species. In healthy cells, bioenergetically compromised mitochondria are removed from the cells (mitophagy), which involves the PINK1/parkin pathway. Mitochondrial functioning additionally relies on Ca2+, which is required for several mitochondrial dehydrogenases. Disruption of either mitophagy or Ca2+ signalling has been implicated in PD pathology.In this study, Mrudula Dileep, Anamika Sharma, Gaiti Hasan and their colleagues investigated whether sporadic PD could arise from convergent toxicity caused by compromised PINK1/parkin and intracellular Ca2+ signalling pathways in dopaminergic neurons. The authors performed experiments using Drosophila carrying mutations in the genes encoding Parkin and the Inositol 1,4,5-trisphosphate receptor (an intracellular Ca2+ channel located on the endoplasmic reticulum), identifying a strong interaction between the encoding genes, which impaired the function of dopaminergic neurons. Single-copy mutations in either gene alone had minimal impact on mitophagy and neuronal Ca2+ release. However, combining both mutations produced a cumulative deficit that reduced mitochondrial energy production during neuronal depolarisation and led to toxic accumulation of H2O2. The authors further showed that overexpression of the antioxidant catalase partially compensated for this energy deficit by restoring the ATP/ADP ratio. Catalase overexpression rescued neuronal function, likely by removing excess H2O2 produced through dopamine oxidation and an overactive electron transport chain.Together, these findings identify oxidative stress as an early driver of dopaminergic neuron dysfunction in PD and suggest that sustained, uncontrolled oxidative stress contributes to later neurodegenerative phenotypes. The study further implies that individuals carrying recessive mutations affecting mitophagy or intracellular Ca2+ signalling could be at increased risk of developing sporadic PD.

Societal Impact Statement Plants provide oxygen, food, shelter, medicines and environmental services, without which human society could not exist. Tackling pressing and global challenges requires well‐trained plant scientists and plant‐aware individuals. This manifesto provides a practical evidence‐based vision to strengthen plant science education, focused on five strategic priorities. It is relevant to all stakeholders within plant science and beyond: from frontline educators to institutional leaders; from commercial or charitable professionals to entrepreneurs and donors; from individual community members to their legislative representatives. Strengthening plant science education demands concrete actions from all stakeholders, ultimately to the benefit of us all. Summary Plant science education needs urgent attention. Skilled plant scientists are needed to address major environmental and societal challenges, and global communities require plant‐aware professionals to drive impactful policy, research and environmental stewardship. This manifesto was collaboratively generated by a community of educators who gathered to reflect on the state of plant science education. The forward‐facing document provides a clear strategy for plant science education, complementing existing research strategies. Five themes were identified as essential for meeting the evolving needs of plant science, educators and learners: (i) plants must be at the centre of an education that addresses global challenges and societal values; (ii) plant science education must prepare students for their futures using bold and effective pedagogies; (iii) equity, diversity and inclusion must be robustly embedded in educational practices; (iv) local and strategic partnerships (with industry and beyond) are required to strengthen academic education; and (v) plant science educators need resources and opportunities to develop and connect. The manifesto is intended as a framework for change. Educators, funders, publishers, industry representatives, policymakers and all other members of our communities must commit to sustained investment in plant science education. By proactively and collectively embracing the recommendations provided, the sector has an opportunity to cultivate a new generation equipped with the knowledge, skills and passion to unlock the full potential of photosynthetic organisms.

Age-related macular degeneration (AMD) is a serious eye disease that leads to deterioration of the retina and causes vision loss. It is a genetically complex disease, and while some risk genes have been identified, in many cases it is not clear how these genes contribute to AMD progression. One such gene linked to AMD is HTRA1, which encodes an enzyme that cleaves other proteins and has been associated with vascular problems in the brain. Some work has suggested that HTRA1 could be modulated therapeutically to treat AMD; however, the exact effects this might have remain unclear.To address this, Katschke, van Lookeren Campagne, Jeanne and colleagues investigated the role of HTRA1 in samples from patients with AMD and mouse models. Immunohistochemistry in healthy donor eye tissue showed that HTRA1 protein was present in the basement membrane that supports the retina and expressed at low levels around the light-detecting photoreceptor cells. Conversely, in samples from patients with AMD, HTRA1 was found in the membranous, collagen-rich deposits characteristic of AMD and accumulated at higher levels around the photoreceptors. To assess whether HTRA1 drives AMD, the authors generated transgenic mouse models overexpressing either a functional or enzymatically inactive version of HTRA1 in the layer of epithelial cells supporting the retina. Overexpression of functional HTRA1 caused decreased retinal thickness and photoreceptor degeneration, reflecting AMD pathology. This was not observed in the absence of HTRA1’s enzymatic activity, suggesting that degeneration is driven by HTRA1’s function. The authors also tested whether HTRA1 activity impacted the retina’s ability to recover from laser-induced damage, which mimics blood vessel invasion often seen in later stages of AMD. These lesions grew larger in the presence of overexpressed HTRA1, suggesting that its activity promotes vascular growth in the retina. Finally, they investigated the pathways through which HTRA1’s enzymatic activity could contribute to accelerating AMD. They performed immunoprecipitation experiments to find proteins that interact with functional HTRA1 and could therefore be targets of the enzyme. One protein identified was RBP3, which is secreted by photoreceptors and essential for vertebrate vision. They showed that RBP3 is indeed cleaved by HTRA1, suggesting that HTRA1 activity could promote AMD progression by causing excessive breakdown of an important vision protein, RBP3.Altogether, this work provides new insights into the pathogenesis of AMD with improved mechanistic understanding of a disease risk gene. This understanding is crucial to assess how modulating risk genes could help or hinder treatment strategies.DMM Research or Resources & Methods articles of particular interest or excellence may be accompanied by a short Editor's choice highlight, selected by a DMM editor and written by either members of the DMM in-house editorial team or an expert in the field. The Editor's choice aims to outline the challenges that the work addresses and how the work advances our insight into disease mechanism, therapy or diagnosis.

The British Society for Cell Biology (BSCB), established in 1965, is a charitable organisation that 'aims to promote research and exchange of information relating to all branches of cell biology'. The Society hosts and supports meetings and conferences relevant to cell biology and plays a crucial role in raising awareness towards scientific policies in the UK and Ireland. Since its early days, the society has held strong ties with The Company of Biologists, a not-for-profit publisher that strives to inspire biology and support biologists. In this Essay, to commemorate the 100-year anniversary of The Company of Biologists, I discuss the evolution of the BSCB and highlight its relationship with the Company from when the Society was founded through to the present day.

Duchenne muscular dystrophy (DMD) is a hereditary neuromuscular disorder that primarily affects boys. It is caused by mutations in the gene encoding dystrophin, a protein essential for maintaining the structural integrity of skeletal and cardiac muscles through their connection to the surrounding extracellular matrix. Symptoms of the condition become noticeable at around two to three years of age and gradually progress, leading to reliance on a wheelchair during teenage years and premature death from cardiorespiratory failure in the second or third decade of life. Although several promising treatments are currently in clinical trials, there is no cure for DMD.The progression of the disease is usually monitored by functional assessments that track changes in mobility and quality of life. However, guidelines for conducting these tests are not well-defined for animal models, resulting in high variability depending on the assessor. To address this problem, Kamila Karimjee and colleagues focused on identifying suitable biomarkers for planned preclinical trials by using the DE50-MD canine model of DMD. In contrast with commonly used mouse models (that exhibit a milder version of the disorder), canine models of DMD more closely reflect the human condition, making them more clinically relevant. The model used in this study carries a spontaneous splice-site mutation resulting in deletion of exon 50 within dystrophin transcripts – which is central to the hotspot for human DMD mutations – and exhibits typical features of muscular dystrophy, including progressive muscle weakness, muscle fibrosis and skeletal muscle wasting. To reduce manual effort and the data bias related to the involvement of the assessor, Kamila Karimjee and colleagues proposed using collar-based accelerometers integrated with their acceleration threshold-based metrics, to quantify changes in activity patterns during disease progression. Because the proposed approach is non-invasive and can be carried out on dogs remaining in their usual environment, it minimises human influence on results and enables a longer-term assessment of the animals' capacity for movement. Moreover, the acceleration threshold method enables the distinction between time spent at different intensity levels of activity, which is not only useful in assessing the effect of investigated treatment on functional outcomes and overall quality of life but also allows comparing results between studies and ensures reproducibility of the work. Kamila Karimjee and colleagues also demonstrated that their approach enables the collection of data during long-term activity monitoring. This allows for discrimination between genotypes and may be applicable for other canine models of DMD, and even in other animal models of diseases associated with locomotor or neuromuscular dysfunction.

ABSTRACTDisease Models & Mechanisms (DMM) is delighted to announce that the winners of the DMM Outstanding Paper Prize 2024 are Destynie Medeiros, Karen Ayala Baylon, Hailey Egido-Betancourt, Christopher Chapleau and Wei Li for their Research Article (titled ‘A small-molecule TrkB ligand improves dendritic spine phenotypes and atypical behaviours in female Rett syndrome mice’), and Jasmin Scheurer and Birgit Sauer for their Resources & Methods article (titled ‘Histological and functional characterization of 3D human skin models mimicking the inflammatory skin diseases psoriasis and atopic dermatitis’). The two prizes of £1000 are awarded to the first author(s) of the papers that are judged by the journal's Editors to be the most outstanding contribution to the journal that year.

Summary: Journal of Cell Science's publisher, The Company of Biologists, is celebrating its 100th birthday in 2025. Here, we review JCS's history since being founded as the Quarterly Journal of Microscopical Sciences.

The lower jaw is a crucial in everyday functions, such as chewing and communication as well as being an aesthetically important part of the face. Resection owing to cancer treatment or injury may result in the loss of jaw parts, affecting the patient's quality of life. Jaw restoration surgery is often technically challenging, which drives interest in new therapeutic strategies. One research approach for this is to investigate highly regenerative processes in model organisms that are known to be able to fully regenerate their amputated limbs – such as the axolotl.For their study, Kramer, Aires, Sandoval-Guzmán and colleagues removed part of the axolotl's lower jaw, including skin, muscle, oral mucosa and connective tissue, and observed the regeneration process over 90 days. The authors also performed RNA sequencing to determine the change in gene expression patterns and their corresponding actions in the regenerating tissue. During the early stages of regeneration, the authors observed wound closure and the expression of genes connected with muscle contraction and maturation. By 14 days post injury (dpi) the site of injury had significantly reduced, yielding a blastema, i.e. the aggregation of cells with the ability to differentiate into different body parts. The authors determined that, at this stage, the regenerating lower jaw tissues strongly expressed genes related to cell adhesion and migration, extracellular matrix disassembly and organisation, and immune response. After 35 dpi, the defect was visually undetectable, and genes related to cartilage formation, intramembranous ossification and regeneration of blood vessels were found to be upregulated. At 35 dpi, the perimeter of the regenerated lower jaw was just 9.2% smaller than the intact control at 90 dpi and contained regenerated teeth.The authors then compared their RNA sequencing data obtained from the regenerating mandible with previously published data relating to the regenerating limb of the axolotl. They found that ∼70% of genes present in lower jaw regenerating tissues was also present in regenerating limb tissues, especially during early and mid-stages of regeneration, thereby indicating common regenerative mechanisms within body parts of different embryonic origin in axolotl.This study highlights key mechanisms of regeneration in the highly regenerative model organism, the axolotl. It provides insight regarding limitations of limb regeneration in humans, and points to potential therapeutic targets for regenerative medicine.