Issues
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Cover image
Cover Image
Cover: Induction of neurite extension after overexpression of wild-type neuroligin 3 (NLGN3) in GN11 cells. Human hemagglutinin (HA)-tagged NLGN3 was expressed in the neuronal gonadotropin-releasing hormone (GnRH)-secreting mouse GN11 cell line. Cells were immunostained for HA (yellow) and phalloidin (purple) to, respectively, detect NLGN3 and actin. Nuclei (cyan) were counterstained with DAPI. See article by Oleari et al. (dmm049996 ). Cover image is licensed under a Creative Commons Attribution 4.0 International license .
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EDITORIAL
A MODEL FOR LIFE
PERSPECTIVE
Hacking hematopoiesis – emerging tools for examining variant effects
Summary: Thousands of genomic loci have been linked to hematopoietic traits and diseases, yet many await functional validation. Here, we discuss recent advances in genome editing and challenges in using these techniques to assess variant function in primary hematopoietic cells.
REVIEW
Translating non-coding genetic associations into a better understanding of immune-mediated disease
Summary: The success of genetic studies provides a unique opportunity to better understand immune-mediated disease mechanisms. To achieve this, however, knowledge of where disease-associated variants lie must be translated into an understanding of how they cause disease.
EDITOR'S CHOICE
RESEARCH ARTICLES
A Drosophila chemical screen reveals synergistic effect of MEK and DGKα inhibition in Ras-driven cancer
Summary: Using a Drosophila Ras-driven cancer model, inhibitors of diacyl glycerol kinase α (DGKα) were identified as being synergistic with low doses of the Ras pathway inhibitor, trametinib.
HuR modulation counteracts lipopolysaccharide response in murine macrophages
Summary: This extensive study provides progress in the development of synthetic modulators of HuR functions, their genome-wide mechanism of action and their activity as anti-inflammatory agents.
Autism-linked NLGN3 is a key regulator of gonadotropin-releasing hormone deficiency
Summary: This study shows, for the first time, a role for NLGN3 in GnRH neuritogenesis and reveals a common genetic mechanism between GnRH deficiency and autism, by applying a combined multiomic approach.
FZD2 regulates limb development by mediating β-catenin-dependent and -independent Wnt signaling pathways
Summary: Limb defects in Robinow syndrome are associated with mutations in FZD2. Using mouse models, we show that FZD2 is causative, and controls limb development via both canonical and non-canonical Wnt pathways.
Dual mechanism underlying failure of neural tube closure in the Zic2 mutant mouse
Summary: We identify a dual mechanism of spina bifida in Zic2 mutant mice – a possible paradigm for multifactorial human defects. BMP overactivation prevents neuroepithelial bending, whereas RhoA overactivation causes actomyosin accumulation.
Activated PI3K delta syndrome 1 mutations cause neutrophilia in zebrafish larvae
Summary: This study uses zebrafish embryos and homology-directed gene editing to investigate the effect of activated PI3 kinase delta syndrome 1 mutations on innate immune cells, observing neutrophilia without defects in neutrophil differentiation or migration.
Impaired episodic-like memory in a mouse model of Alzheimer's disease is associated with hyperactivity in prefrontal–hippocampal regions
Summary: Using a preclinical Alzheimer's disease model, our work highlights that episodic memory impairment at early disease stage is associated with neuronal hyperactivity in specific medial prefrontal cortex and hippocampus regions.
A hepatoprotective role of peritumoral non-parenchymal cells in early liver tumorigenesis
Editor's choice: Our work using in vitro liver spheroid models consisting of both parenchymal and non-parenchymal cells shows a hepatoprotective role of peritumoral hepatic stellate cells in liver tumorigenesis.
RESOURCE ARTICLES
In vivo quantitative high-throughput screening for drug discovery and comparative toxicology
Summary: We describe an in vivo quantitative high-throughput screening strategy with C. elegans, designed to leverage and engage experience of the model organism community with screening and drug development resources.
Tellu – an object-detector algorithm for automatic classification of intestinal organoids
Summary: Description and demonstration of an automated easy-to-use online tool for classifying intestinal organoids to facilitate quantitative analyses of increasingly popular organoids.
FIRST PERSON
CORRECTION
Sex matters in preclinical research
DMM calls for improved inclusion, analysis and reporting of sex as a biological variable in preclinical animal modelling research. Read the full Editorial by Monica J. Justice.
Subject collection: Building advocacy into research
DMM’s new series - Building advocacy into research - features interviews, ‘The Patient’s Voice’, with patients and advocates for a range of disease types, with the aim of supporting the highest quality research for the benefit of all patients affected by disease.
Travelling Fellowships for early-career researchers
DMM and its sister journals offer Travelling Fellowships of up to £3,000 to graduate students and post-doctoral researchers wishing to make collaborative visits to other laboratories. Find out more about our Travelling Fellowships and read stories from previous grant recipients.
Read & Publish Open Access publishing: what authors say
We have had great feedback from authors who have benefitted from our Read & Publish agreement with their institution and have been able to publish Open Access with us without paying an APC. Read what they had to say.
The Forest of Biologists
Our Publisher Claire Moulton recently visited the two Woodland Trust UK sites where we are planting new native trees for published Research and Review papers and protecting ancient woodland on behalf of our peer reviewers.