Cover: Malignant gliomas including glioblastomas are extremely infiltrative, and complete surgical resection is almost impossible. Understanding the molecular mechanisms of tumour cell infiltration and developing anti-invasive approaches are of the utmost priority. Using mCherry-labelled rat C6 malignant glioma cells and kdrl:EGFP transgenic zebrafish, Ai et al. (dmm049109) visualised the extensive infiltration of the implanted glioma cells along the cerebral capillaries in the zebrafish brain at single-cell resolution, providing a powerful animal model for studying the mechanism of intracranial infiltration of malignant glioma and screening of anti-invasive drugs. Cover image is licensed under a Creative Commons Attribution 4.0 International license.
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DMM Outstanding Paper Prize 2021 winner: Daniel Bronder
Summary: DMM announces Daniel Bronder as the winner of the 2021 DMM Outstanding Paper Prize.
The benefits, limitations and opportunities of preclinical models for neonatal drug development
Summary: This article reviews and analyzes the available preclinical models for five common neonatal diseases to direct therapeutic development in these areas of high unmet medical need.
The clinical manifestations, molecular mechanisms and treatment of craniosynostosis
Summary: Craniosynostosis has broad clinical manifestations and a complex etiology. We review studies from humans and animal models and discuss the developmental mechanisms of craniosynostosis and potential mesenchymal stem cell-based suture regeneration therapeutic strategies.
New Drosophila models to uncover the intrinsic and extrinsic factors that mediate the toxicity of the human prion protein
Summary: New Drosophila models of prion diseases show the high toxicity of human PrP compared to rodent PrP and identify genetic modifiers and protective residues.
Auriculocondylar syndrome 2 results from the dominant-negative action of PLCB4 variants
Summary: PLCB4 variants associated with auriculocondylar syndrome act in a dominant-negative manner to cause craniofacial defects that include both homeotic and atavistic changes in mice and humans.
Physiological tissue-specific and age-related reduction of mouse TDP-43 levels is regulated by epigenetic modifications
Summary: Identification of a cause-effect relationship between epigenetic modifications that occur on the promoter and histones of mouse TARDBP and the level of TDP-43 both in tissues and in cell culture.
Development of a novel human intestinal model to elucidate the effect of anaerobic commensals on Escherichia coli infection
Summary: The new model system established in this study enables culture of human mucus-producing intestinal epithelia with oxygen-sensitive gut commensals and characterization of their effects on enteropathogenic E. coli infection.
TDP-43 promotes tau accumulation and selective neurotoxicity in bigenic Caenorhabditis elegans
Summary: TDP-43 co-pathology is a frequent feature of Alzheimer's disease. This paper shows that TDP-43 specifically enhances tau neurotoxicity, but not amyloid β, to promote pathological protein accumulation, behavioral impairment and selective neurodegeneration.
The Paget's disease of bone risk gene PML is a negative regulator of osteoclast differentiation and bone resorption
Summary:PML, a susceptibility gene for Paget's disease of bone, is a novel negative regulator of bone metabolism. The differentiation of osteoclasts and osteoblasts is enhanced in Pml−/− mice compared with controls.
Adipose tissue-specific ablation of PGC-1β impairs thermogenesis in brown fat
Summary: Adipose tissue-specific ablation of PGC-1β impairs thermogenesis in murine brown fat owing to a reduced number of contacts between mitochondria and lipid droplets, possibly involving the L-form of optic atrophy 1 protein.
Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease
Summary: Macrophages contribute to both progression and resolution of chronic tissue injury and fibrogenesis. Administration of a macrophage growth factor promoted liver regeneration and resolution of advanced liver fibrosis in mice.
A novel yeast model detects Nrf2 and Keap1 interactions with Hsp90
Summary: We studied the interactions of human Nrf2 in a novel budding yeast model. We recapitulate previously described Nrf2 interactions and discover that Nrf2 interacts with Hsp90, establishing yeast as a useful tool to study Nrf2 interactions.
A zebrafish reporter line reveals immune and neuronal expression of endogenous retrovirus
Summary: Characterisation of the zebrafish endogenous retrovirus zferv reveals expression in early T cells and neurons, highlighting a potential role of endogenous retroviruses in brain development and immune disorders.
Clinically relevant orthotopic xenograft models of patient-derived glioblastoma in zebrafish
Editor's choice: We established zebrafish glioblastoma (GBM) xenograft models that can be used to perform genetic and biological analysis of GBMs, identify blood–brain barrier-penetrating drugs and predict clinical sensitivity to temozolomide in GBM patients.
A dog model for centronuclear myopathy carrying the most common DNM2 mutation
Summary: Description of a spontaneous dog model and generation of a cohort carrying the most common DNM2 mutation associated with autosomal dominant centronuclear myopathy in humans.
DMM Journal Meeting 2023: Infectious Diseases Through an Evolutionary Lens
The abstract submission deadline for our 2023 Journal Meeting ‘Infectious Diseases Through an Evolutionary Lens’ is 14 July 2023. Find out more and register here.
The Forest of Biologists
The Forest of Biologists is a biodiversity initiative created by The Company of Biologists, with support from the Woodland Trust. For every Research and Review article published in Disease Models & Mechanisms a native tree is planted in a UK forest. In addition to this we are protecting and restoring ancient woodland and are dedicating these trees to our peer reviewers. Visit our virtual forest to learn more.
Propose a new Workshop for 2025
Do you have an idea for a Workshop? If so, click here. We are now accepting proposals for our 2025 Workshops programme. As the scientific organiser, your involvement will be focused on the science. We'll take care of all the logistics. In 2025 we'll continue our efforts to diversify our Workshop programme and will be reserving one of our Workshops for an application from a Global South country to host an event overseas.
How stromal cells restrict liver cancer invasion
In our recent editor’s choice, Liqin Zhu and colleagues describe how they used in vitro liver spheroid models consisting of both parenchymal and non-parenchymal cells to reveal a hepatoprotective role for peritumoral hepatic stellate cells in liver tumorigenesis.
And from perspective… Hacking haematopoiesis – emerging tools for examining variant effects
Thousands of genomic loci have been linked to hematopoietic traits and diseases, yet many await functional validation. Michael Gundry and Vijay G. Sankaran discuss recent advances in genome editing and the challenges associated with using these techniques to assess variant function in primary hematopoietic cells. a celebration of the achievements of female scientists, and a call to action for a culture shift in science.