Cover: A section through the trigeminal ganglion of a 1-week-old mouse pup carrying a heterozygous deletion of 28 genes on mouse Chromosome 16 that is orthologous to the deletion associated with the human developmental disorder 22q11.2 deletion/DiGeorge syndrome. The deletion alters interactions between neural crest-derived (green) and placode-derived cells early in embryogenesis, leading to changes in the proportions and molecular identities of nociceptive neurons, a subset of which is labelled for the neurotrophin receptor TrkA (red). See article by Karpinski et al. (dmm047357). Cover image is licensed under a Creative Commons Attribution 4.0 International license.
- PDF Icon PDF LinkTable of contents
- PDF Icon PDF LinkIssue info
Special Issue: The RAS Pathway
Understanding and drugging RAS: 40 years to break the tip of the iceberg
Summary: This Editorial introduces DMM’s new Special Issue on the RAS pathway. The Guest Editors reflect on the impact of the featured articles on the landscape of the RAS field.
A MODEL FOR LIFE
Summary: RASopathy is a term used to unify a phenotypically similar group of medical genetic syndromes, yet its definition is challenging and should consider the perspectives of clinicians, scientists and the patients.
RAS and beyond: the many faces of the neurofibromatosis type 1 protein
Summary: Neurofibromatosis type 1 has provided unprecedented opportunities to define the importance of RAS regulation in health and disease. Emerging research has also unveiled the role of non-canonical RAS and RAS-independent signaling in this RASopathy.
RAS pathway regulation in melanoma
Summary: This Review describes the molecular regulation of the RAS pathway, presents the clinical consequences of its pathological activation in human cancer, and highlights recent advances towards its therapeutic inhibition, using melanoma as an example.
The RASopathies: from pathogenetics to therapeutics
Summary: RASopathies are developmental disorders caused by germline pathogenic variants in RAS/MAPK pathway genes. Here, we review the preclinical studies that provide the basis for future interventional clinical trials for RASopathy patients.
RAS-mediated tumor stress adaptation and the targeting opportunities it presents
Summary: The acquisition of oncogenic RAS simultaneously causes cellular stress and activates stress-adaptive pathways. Many of these are implicated in resistance mechanisms to RAS-targeting therapies, posing as therapeutic targets to block stress-activated mechanisms of resistance.
Analysis of the H-Ras mobility pattern in vivo shows cellular heterogeneity inside epidermal tissue
Summary: Single-molecule microscopy analysis of factors altering the in vivo dynamics of H-Ras proteins in epidermal cells in living zebrafish embryos revealed that cell architecture and protein activation state determine protein mobility.
Ras signaling and RREB1 are required for the dissociation of medial edge epithelial cells in murine palatogenesis
Summary: RREB1, a known transcriptional factor that acts downstream of Ras signaling, is expressed in the medial edge epithelium (MEE) region and required for the dissociation of MEE during palatal fusion.
Statins mediate anti- and pro-tumourigenic functions by remodelling the tumour microenvironment
Summary: Characterisation of mouse lung adenoma/adenocarcinoma models treated with atorvastatin revealed that statins remodel the tumour microenvironment in lung adenocarcinoma development to create pro- and anti-tumourigenic effects dependent on disease stage.
MEK-inhibitor-mediated rescue of skeletal myopathy caused by activating Hras mutation in a Costello syndrome mouse model
Summary: A Costello syndrome (CS) mouse model carrying a heterozygous Hras p.G12V mutation was utilized to investigate Ras pathway dysregulation, revealing that increased MAPK signaling is the main cause of the muscle phenotype in CS.
Pharmacological or genetic inhibition of hypoxia signaling attenuates oncogenic RAS-induced cancer phenotypes
Summary: Hypoxia pathway inhibition, either genetically or pharmacologically, rescues RAS-induced oncogenesis in a Drosophila acute myeloid leukemia model, mouse xenograft model and human leukemia cells.
Tissue architecture delineates field cancerization in BRAFV600E-induced tumor development
Summary: This study investigates how a BRAF-mutant lineage becomes cancerized by escaping cell competition from non-mutant cells in a mouse model of sporadic thyroid cancer.
Selective disruption of trigeminal sensory neurogenesis and differentiation in a mouse model of 22q11.2 deletion syndrome
Summary: Altered proportions, distribution, timing and modes of division for trigeminal ganglion progenitors prefigure divergent trigeminal sensory neuron differentiation and oropharyngeal dysfunction in the LgDel mouse model of 22q11.2 deletion syndrome.
K-Ras and p53 mouse model with molecular characteristics of human rhabdomyosarcoma and translational applications
Editors' choice: We developed a new conditional genetically engineered mouse model of rhabdomyosarcoma (RMS) with homologous molecular signature to human RMS that provides valuable pre-clinical models for evaluating novel therapies.
DMM Journal Meeting 2023: Infectious Diseases Through an Evolutionary Lens
We are delighted to announce that our 2023 Journal Meeting ‘Infectious Diseases Through an Evolutionary Lens’ will be held from 17-19 October 2023 in London, UK. Registration is open now.
The Forest of Biologists
We are excited to announce the launch of The Forest of Biologists, a new biodiversity initiative created with support from the Woodland Trust, aiming to counteract nature loss and safeguard some of the most critically endangered ecosystems for future generations. For every Research Article and Review article that is published in one of our five journals a native tree is planted in a forest in the UK. Take a look at our virtual forest online now.
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 Biologists 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 (GS) country to host an event overseas.
New drugs to squash the spread of malaria
In this Research Article, the Baum lab identify a new class of antimalarials to block Plasmodium gamete formation. This article has been highlighted as our Editor’s Choice, and you can find out more in our interview with first author Sabrina Yahiya.
The shifting culture of the scientific workforce – a change for women and girls in science
February 11 marks The International Day of Women and Girls in Science (IDWGS) a celebration of the achievements of female scientists, and a call to action for a culture shift in science. Click here to read more about the day