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Tissue growth needs to be properly controlled for organs to reach their correct size and shape, but the mechanisms that control growth during normal development are not fully understood. We report here that the activity of the Hippo signaling transcriptional activator Yorkie gradually decreases in the central region of the developing wing disc. Spatial and temporal changes in Yorkie activity can be explained by changes in cytoskeletal tension and biomechanical regulators of Hippo signaling. These changes in cellular biomechanics correlate with changes in cell density, and experimental manipulations of cell density are sufficient to alter biomechanical Hippo signaling and Yorkie activity. We also relate the pattern of Yorkie activity in older discs to patterns of cell proliferation. Our results establish that spatial and temporal patterns of Hippo signaling occur during wing development, that these patterns depend upon cell-density modulated tissue mechanics and that they contribute to the regulation of wing cell proliferation.
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http://dx.doi.org/10.1242/dev.165712 | DOI Listing |
Elife
September 2025
Center for Autoimmune Genomics and Etiology, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States.
Human cytomegalovirus (HCMV) infects up to 80% of the world's population. Here, we show that HCMV infection leads to widespread changes in human chromatin accessibility and chromatin looping, with hundreds of thousands of genomic regions affected 48 hr after infection. Integrative analyses reveal HCMV-induced perturbation of Hippo signaling through drastic reduction of TEAD1 transcription factor activity.
View Article and Find Full Text PDFJ Cell Physiol
September 2025
Jiangxi Province Key Laboratory of Immunology and Inflammation, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Ovarian granulosa cells (GCs) are pivotal for follicular homeostasis, and their dysregulated apoptosis drives age-related ovarian aging. The Hippo signaling pathway, modulated by long noncoding RNAs (lncRNAs), is implicated in regulating GCs proliferation and ovarian aging. TEAD2 (Transcriptional Enhanced Associate Domain 2), a key downstream transcription factor of the Hippo signaling pathway, plays a critical role in regulating cell proliferation, apoptosis, and embryonic stem cell self-renewal.
View Article and Find Full Text PDFAging Cell
September 2025
Department of Cell Systems & Anatomy, University of Texas Health San Antonio, San Antonio, Texas, USA.
The Hippo signaling pathway is a key regulator of cell growth and cell survival, and hyperactivation of the Hippo pathway has been implicated in neurodegenerative diseases such as Huntington's disease. However, the role of Hippo signaling in Alzheimer's disease (AD) remains unclear. We observed that hyperactivation of Hippo signaling occurred in the AD model 5xFAD mice.
View Article and Find Full Text PDFPurpose: Combinatorial therapies are essential for treating advanced non-small cell lung cancer (NSCLC), particularly overcoming resistance to third-generation epidermal growth factor receptor (EGFR) like osimertinib (OSI). The Hippo signaling pathway, a critical regulator of cell proliferation, apoptosis, and tumor progression, is often dysregulated in NSCLC and contributes to chemo-resistance. This study investigated the potential of epigallocatechin-3-gallate (EGCG), a green tea polyphenol, to overcome OSI resistance by modulating the Hippo signaling pathway, specifically through inhibition of the YAP-1 (Yes-associated protein)-TEAD (TEA domain transcription factor)-CTGF (connective tissue growth factor) axis.
View Article and Find Full Text PDFJ Environ Pathol Toxicol Oncol
September 2025
Department of Clinical Laboratory Medicine, Fujian Medical University, Fuzhou, China.
Invasive ductal carcinoma (IDC) is a major type of breast cancer. The utilization of inhibitors targeting histone methyltransferases introduces novel therapeutic avenues for the treatment of cancer. Immunohistochemistry, Western blot, and reverse transcription quantitative polymerase chain reaction experiments were applied to assess the levels of EHMT2 in IDC and adjacent tissues.
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