Predicting human disease mutations and identifying drug targets from mouse gene knockout phenotyping campaigns
Summary: Large-scale, focused phenotyping campaigns provide data for thousands of mutant mouse genes, yielding key information for understanding rare human diseases and for developing novel drug therapies.
Summary: This Review summarizes some of the exciting work that has used Drosophila as a model for the ever-expanding field of intellectual disability and autism spectrum disorders. It highlights disease-relevant assays, emerging themes and future challenges.
Enhancer of Polycomb and the Tip60 complex repress hematological tumor initiation by negatively regulating JAK/STAT pathway activity
Editor's choice: Using Drosophila as a low-complexity model for human myeloproliferative neoplasms, the authors identified a conserved mechanism by which the Tip60 lysine acetyltransferase acts as a tumor suppressor by repressing JAK protein expression in a histone-independent manner.
Mandibular dysmorphology due to abnormal embryonic osteogenesis in FGFR2-related craniosynostosis mice
Summary: FGFR2 gain-of-function mutations differentially affect cartilage formation and intramembranous ossification of dermal bone, resulting in abnormal embryonic osteogenesis of the mandible.
Glucocorticoids inhibit macrophage differentiation towards a pro-inflammatory phenotype upon wounding without affecting their migration
Summary: In a zebrafish model for inflammation, glucocorticoids do not affect the migration of macrophages, but inhibit their differentiation towards an M1 phenotype, by strongly attenuating transcriptional responses in these cells.
Effects of subthalamic deep brain stimulation on striatal metabolic connectivity in a rat hemiparkinsonian model
Summary: Deep brain stimulation in the subthalamic nucleus in rats with a unilateral dopaminergic lesion established a new functional interhemispheric striatal network.
Summary: The roles of DYRK1A in angiogenesis and maintenance of the developing cerebral vasculature mediated by calcium signaling were revealed using zebrafish dyrk1aa knockout mutants.
Inhibition of the IGF-1–PI3K–Akt–mTORC2 pathway in lipid rafts increases neuronal vulnerability in a genetic lysosomal glycosphingolipidosis
Summary: The authors present a mechanistic model to understand how alterations of the membrane architecture by the progressive accumulation of sphingolipids undermines basic cell function, with potential implications for a variety of genetic sphingolipidoses and adult neurodegenerative conditions.
Amyotrophic lateral sclerosis mutant TDP-43 may cause synaptic dysfunction through altered dendritic spine function
Summary: Loss of synaptic GluR1, and reduced excitability within pyramidal neurons, implicates hypoexcitability and attenuated synaptic function in the pathogenic decline of neuronal function in TDP-43-associated ALS.
Adenosine and hyaluronan promote lung fibrosis and pulmonary hypertension in combined pulmonary fibrosis and emphysema
Summary: Fibrotic deposition and PH are inhibited by the FDA-approved drug hymecromone, suggesting hyaluronan synthesis inhibition as a potential therapy for CPFE and highlighting a novel mechanism through HAS3-positive macrophages.
Summary: Homozygous loss of asxl1 in zebrafish leads to apoptosis of newly formed HSCs by upregulation of bim and bid. Half of the asxl1+/− zebrafish had MPNs by 5 months of age.
Beneficial effects of exercise on gut microbiota functionality and barrier integrity, and gut-liver crosstalk in an in vivo model of early obesity and non-alcoholic fatty liver disease
Summary: The beneficial effects of exercise against diet-induced early obesity and NAFLD are mediated by its capacity to modulate intestinal microbiota composition and functionality, restore lipid metabolism and prevent disruption of the gut-liver axis.