Animal development is characterized by signaling events that occur at precise locations and times within the embryo, but determining when and where such precision is needed for proper embryogenesis has been a long-standing challenge. Here we address this question for extracellular signal regulated kinase (Erk) signaling, a key developmental patterning cue. We describe an optogenetic system for activating Erk with high spatiotemporal precision in vivo. Implementing this system in Drosophila, we find that embryogenesis is remarkably robust to ectopic Erk signaling, except from 1 to 4 hr post-fertilization, when perturbing the spatial extent of Erk pathway activation leads to dramatic disruptions of patterning and morphogenesis. Later in development, the effects of ectopic signaling are buffered, at least in part, by combinatorial mechanisms. Our approach can be used to systematically probe the differential contributions of the Ras/Erk pathway and concurrent signals, leading to a more quantitative understanding of developmental signaling.
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http://dx.doi.org/10.1016/j.devcel.2016.12.002 | DOI Listing |
Sci Rep
January 2025
Key Laboratory for Stem Cells and Tissue Engineering Ministry of Education, Guangdong Provincial Key Laboratory of Brain Function and Disease, Institute of Spinal Cord Injury, Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Neuromuscular diseases usually manifest as abnormalities involving motor neurons, neuromuscular junctions, and skeletal muscle (SkM) in postnatal stage. Present in vitro models of neuromuscular interactions require a long time and lack neuroglia involvement. Our study aimed to construct rodent bioengineered spinal cord neural network-skeletal muscle (NN-SkM) assembloids to elucidate the interactions between spinal cord neural stem cells (SC-NSCs) and SkM cells and their biological effects on the development and maturation of postnatal spinal cord motor neural circuits.
View Article and Find Full Text PDFPLoS One
January 2025
Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, China.
Hepatocellular carcinoma(HCC) has a high mortality and morbidity rate and seriously jeopardizes human life. Chemicals and chemotherapeutic agents have been experiencing problems such as side effects and drug resistance in the treatment of HCC, which cannot meet the needs of clinical treatment. Therefore, finding novel low-toxicity and high-efficiency anti-hepatocellular carcinoma drugs and exploring their mechanisms of action have become the current problems to be solved in the treatment of HCC.
View Article and Find Full Text PDFElife
January 2025
Centre for Cellular Biology and Signalling, Zhejiang University-University of Edinburgh (ZJU-UoE) Institute, Haining, China.
Mitochondrial dysfunction is involved in numerous diseases and the aging process. The integrated stress response (ISR) serves as a critical adaptation mechanism to a variety of stresses, including those originating from mitochondria. By utilizing mass spectrometry-based cellular thermal shift assay (MS-CETSA), we uncovered that phosphatidylethanolamine-binding protein 1 (PEBP1), also known as Raf kinase inhibitory protein (RKIP), is thermally stabilized by stresses which induce mitochondrial ISR.
View Article and Find Full Text PDFArch Endocrinol Metab
January 2025
Universidade Estadual Paulista Faculdade de Medicina de Botucatu BotucatuSP Brasil Universidade Estadual Paulista, Faculdade de Medicina de Botucatu, Botucatu, SP, Brasil.
Objective: Considering that the αvβ3 integrin plays an important role in tumor metastasis, this study investigated the involvement of these pathways in mediating the triiodothyronine (T3) effects on amphiregulin () expression.
Materials And Methods: We treated MCF-7 cells with T3 (10 nM) for 1 hour in the presence or absence of inhibitors for αvβ3 integrin (RGD peptide), MAPK (PD98059), PI3K (LY294002), and protein synthesis (cycloheximide [CHX]). A control group (C) received no T3 or inhibitors.
FEBS J
January 2025
Department of Urology, Renmin Hospital of Wuhan University, China.
In our research, we constructed models of renal ischemia-reperfusion (I/R)-exposed acute kidney injury (AKI) and unilateral ureteral obstruction (UUO)-stimulated renal fibrosis (RF) in C57BL/6 mice and HK-2 cells. We firstly authenticated that oral pinocembrin (PIN) administration obviously mitigated tissue damage and renal dysfunction induced by I/R injury, and PIN attenuated UUO-caused RF, as confirmed by the reduced expression of fibrotic markers as well as hematoxylin-eosin (H&E), Sirius red, immunohistochemistry, and Masson staining. Meanwhile, the beneficial role of PIN was again demonstrated in HK-2 cells with hypoxia-reoxygenation (H/R) or transforming growth factor beta-1 (TGF-β1) treatment.
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