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During embryo development, concentration gradients of signalling molecules instruct formation of different cell types. How these gradients adapt to variable embryo sizes to form a properly scaled individual remains elusive. A simple system of an activator and an inhibitor, with different diffusion properties, may give an answer.
Chan Wah Hak et al. show how plasma membrane patches are primed for fast endophilin-mediated endocytosis and disassembly, in the absence of receptor stimulation, through FBP17 and CIP4 binding to SHIP2 and lamellipodin.
Lawrence et al. show that mTORC1 capture and activation at the lysosome are regulated by nutrients that destabilize Rag GTPase–Ragulator binding, and delineate how cancer-specific Rag mutants increase mTORC1 signalling.
Almuedo-Castillo et al. show that extirpated embryos are reduced in size but exhibit normal proportions. Following a computational screen, the authors identify an increased concentration of the Nodal inhibitor Lefty to be responsible for the size scaling.
A previously unidentified protein complex termed Shieldin acts with the nucleosome-binding protein 53BP1 to limit end resection at DNA double-strand breaks, impacting myriad biological outcomes, from immunology to cancer therapy, and highlighting the importance of chromatin responses to DNA damage in vertebrates.
Skeletal muscle denervation leads to myofibre atrophy with fibrosis and fatty infiltration of muscle-resident fibroadipogenic progenitors (FAPs). A study shows that on denervation, FAPs activate pathogenic STAT3–IL-6 signalling. Inhibition of this pathway prevents atrophy and points to potential therapeutic targets.
Understanding the dynamics and complexity of tumour metastasis is crucial for improving clinical interventions and care for cancer patients. In this issue, we present the first of a Series of commissioned Review articles that discuss emerging concepts, technological advances and therapeutic implications in this exciting field.
Stefano Piccolo and co-authors review recent insights into how YAP and TAZ transcription factors respond to the tissue environment, and how they mediate altered cell behaviour. Feedback mechanisms and crosstalk with other pathways are discussed, as are outstanding questions in the field.
Celia-Terrassa and Kang discuss specialized functions of distinct metastatic niches, and how the emerging knowledge can be leveraged for improved therapeutic opportunities.
Madaro et al. show that denervation induces accumulation of IL-6–STAT3-activated fibro-adipogenic progenitors without inflammation or muscle regeneration, leading to muscle atrophy and fibrosis.
Metastatic colonization of distant organs is the prime cause of mortality from cancer, and is governed by a series of steps that include survival and growth in the perivascular niche. A study now shows that L1CAM is necessary for tight physical interactions in this niche, involving a YAP–MRTF–β1-integrin mechanotransduction pathway.
Enteroendocrine (EE) cells secrete diverse peptide hormones, regulating food intake, digestion and metabolism. A study now challenges the traditional view that each hormone is the dominant product of a distinct EE cell type, showing that in response to local cues the same cell produces different hormones in different tissue compartments.
Beumer et al. show that intestinal enteroendocrine cells adjust their hormonal profile during migration from the crypt to the villus, depending on region-specific BMP signalling.
Sozen et al. devise an approach to combine embryonic stem cells, trophoblast stem cells and extra-embryonic endoderm stem cells into self-assembling embryo-like structures, which recapitulate key hallmarks of gastrulation in vitro.
Massagué and colleagues show that disseminated cancer cells use L1CAM to spread on capillaries and to achieve their outgrowth through activating YAP signalling.