The vertebrate embryo undergoes a series of dramatic morphological changes as the body extends to form the complete anterior-posterior axis during the somite-forming stages. The molecular mechanisms regulating these complex processes are still largely unknown. We show that the Hippo pathway transcriptional coactivators Yap1 and Wwtr1 are specifically localized to the presumptive epidermis and notochord, and play a critical and unexpected role in posterior body extension by regulating Fibronectin assembly underneath the presumptive epidermis and surrounding the notochord. We further find that Yap1 and Wwtr1, also via Fibronectin, have an essential role in the epidermal morphogenesis necessary to form the initial dorsal and ventral fins, a process previously thought to involve bending of an epithelial sheet, but which we now show involves concerted active cell movement. Our results reveal how the Hippo pathway transcriptional program, localized to two specific tissues, acts to control essential morphological events in the vertebrate embryo.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773182 | PMC |
| http://dx.doi.org/10.7554/eLife.31065 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Cell Polarity Protein MPP5/PALS1 Controls the Subcellular Localization of the Oncogenes and in Liver Cancer.
Int J Mol Sci
January 2025
Institute of Pathology, Medical Faculty Heidelberg, Heidelberg University, 69120 Heidelberg, Germany.
The oncogenes yes-associated protein () and transcriptional coactivator with PDZ-binding motif () are potent liver oncogenes. Because gene mutations cannot fully explain their nuclear enrichment, we aim to understand which mechanisms cause activation in liver cancer cells. The combination of proteomics and functional screening identified numerous apical cell polarity complex proteins interacting with YAP and TAZ.
View Article and Find Full Text PDFTargeting breast cancer stem cells in ER-positive breast cancer by repurposing the benzoporphyrin derivative verteporfin as a YAP/TAZ small molecule inhibitor.
Mol Biol Rep
January 2025
Cancer Research Laboratory, Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, West Bengal, 700019, India.
Background: Current treatment strategies for hormone-dependent breast cancers, including adjuvant endocrine therapy, often fail due to persistence of breast cancer stem cells (brCSCs), which are significant contributors to tumor recurrence and treatment resistance. Therefore, gaining deeper insights into the molecular regulators driving breast cancer aggressiveness is important. Moreover, given the complexities and expenses involved in developing new pharmacological agents, the strategic repurposing of existing FDA-approved drugs to target these key molecular pathways presents a compelling approach for identifying novel therapeutic interventions aimed at mitigating tumor refractoriness.
View Article and Find Full Text PDFNoncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis.
Sci Adv
January 2025
Department of Biochemistry, College of Life Science and Biotechnology, Brain Korea 21 Project, Yonsei University, Seoul 03722, Republic of Korea.
Until now, Hippo pathway-mediated nucleocytoplasmic translocation has been considered the primary mechanism by which yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional coactivators regulate cell proliferation and differentiation via transcriptional enhanced associate domain (TEAD)-mediated target gene expression. In this study, however, we found that TAZ, but not YAP, is associated with the Golgi apparatus in macrophages activated via Toll-like receptor ligands during the resolution phase of inflammation. Golgi-associated TAZ enhanced vesicle trafficking and secretion of proinflammatory cytokines in M1 macrophage independent of the Hippo pathway.
View Article and Find Full Text PDFTransient activation of YAP/TAZ confers resistance to morusin-induced apoptosis.
BMC Mol Cell Biol
January 2025
Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Background: The Hippo signaling pathway involves a kinase cascade that controls phosphorylation of the effector proteins YAP and TAZ, leading to regulation of cell growth, tissue homeostasis, and apoptosis. Morusin, a compound extracted from Morus alba, has shown potential in cancer therapy by targeting multiple signaling pathways, including the PI3K/Akt/mTOR, JAK/STAT, MAPK/ERK, and apoptosis pathways. This study explores the effects of morusin on YAP activation and its implications for apoptosis resistance.
View Article and Find Full Text PDFTargeting YAP/TAZ-TEAD signaling as a therapeutic approach in head and neck squamous cell carcinoma.
Cancer Lett
January 2025
Moores Cancer Center, University of California San Diego, La Jolla, CA, USA; Department of Pharmacology, University of California San Diego, La Jolla, CA, USA. Electronic address:
Genetic alterations in Hippo pathway and the consequent activation of YAP/TAZ-TEAD are frequently observed in HPV-negative head and neck squamous cell carcinoma (HNSCC) patients. These include loss-of-function mutation and/or copy number loss of FAT1, and amplification of YAP1 and WWTR1 (encoding TAZ), thus raising the possibility that HNSCC cells may be dependent on YAP/TAZ-TEAD-mediated transcriptional programs. In this regard, the recent development of small molecule TEAD inhibitors (smTEADi) provides an opportunity to therapeutically target Hippo pathway dysregulation in human malignancies.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!