A Yap-dependent transcriptional program directs cell migration for embryo axis assembly
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA833056 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18962859.fastq.gz | Fastqsanger.gz | |||
| SRR18962860.fastq.gz | Fastqsanger.gz | |||
| SRR18962861.fastq.gz | Fastqsanger.gz | |||
| SRR18962862.fastq.gz | Fastqsanger.gz | |||
| SRR18962863.fastq.gz | Fastqsanger.gz |
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Project description:The assembly of the embryo’s primary axis is a fundamental landmark to establish the vertebrate body plan. Although the morphogenetic movements directing cell convergence towards the midline have been described extensively, little is known on how gastrulating cells interpret mechanical cues. Yap proteins are well-known transcriptional mechanotransducers, yet their role in gastrulation remains elusive. Here we show that the double knockout of yap and its paralog yap1b in medaka results in an axis assembly failure, due to reduced displacement and migratory persistence in mutant cells. We identified genes involved in cytoskeletal organization and cell-ECM adhesion, rather than in germ layers specification, as direct Yap targets. Dynamic analysis of live sensors and downstream targets reveal that Yap is acting in migratory cells, in which promotes cortical actin and focal adhesions recruitment. Our results indicate that Yap coordinates a mechano-regulatory loop essential to maintain the directed cell migration sustaining embryo axis development.
2022-05-01 | GSE201791 | GEO
Project description:The assembly of the embryo's primary axis is a fundamental landmark for the establishment of the vertebrate body plan. Although the morphogenetic movements directing cell convergence towards the midline have been described extensively, little is known on how gastrulating cells interpret mechanical cues. Yap proteins are well-known transcriptional mechanotransducers, yet their role in gastrulation remains elusive. Here we show that the double knockout of yap and its paralog yap1b in medaka results in an axis assembly failure, due to reduced displacement and migratory persistence in mutant cells. Accordingly, we identified genes involved in cytoskeletal organization and cell-ECM adhesion as potentially direct Yap targets. Dynamic analysis of live sensors and downstream targets reveal that Yap is acting in migratory cells, promoting cortical actin and focal adhesions recruitment. Our results indicate that Yap coordinates a mechanoregulatory program to sustain intracellular tension and maintain the directed cell migration for embryo axis development.
| S-EPMC10188487 | biostudies-literature
Project description:Hippo effectors YAP/TAZ act as on-off mechanosensing switches by sensing modifications in extracellular matrix (ECM) composition and mechanics. The regulation of their activity has been described so far through a hierarchical model in which elements of Hippo pathway are under the control of Focal Adhesions (FAs). Here we unveiled the molecular mechanism by which cell spreading and RhoA GTPase control FA formation through YAP to stabilize the anchorage of actin cytoskeleton to cell membrane. This mechanism required YAP co-transcriptional function and involved the activation of genes encoding for integrins and FA docking proteins. Tuning YAP transcriptional activity led to the modification of cell mechanics, force development, adhesion strength, determined cell shaping, migration and differentiation. These results provide new insights into the mechanism of YAP mechanosensing activity and qualify Hippo effector as the key determinant of cell mechanics in response to ECM cues.
2017-05-17 | E-MTAB-5217 | biostudies-arrayexpress
Project description:Delineating the mechanisms controlling the invasive spread of non-diseased and transformed cells is central to understanding diverse processes including cancer progression. Here, we found that Yes-associated protein (YAP), a central transcriptional regulator implicated in controlling organ and body size, modulated a Rho-GTPase switch that drives cellular migration by transactivating the Rac1-GEF protein TRIO through direct modulation of its intronic enhancer. Additionally, YAP and TRIO may promote invasive behavior through putative crosstalk with STAT3 signaling, a potential downstream target. Although we found this YAP-dependent infiltrative program in many cell types, it was particularly enhanced in a patient-specific manner in the most common malignant brain tumor, glioblastoma (GBM), where hyperactivation of the YAP, TRIO, and STAT3 signatures also conferred poor clinical outcome. Our analysis suggests that the YAP-TRIO-Rho-GTPase signaling network identified in this study is a ubiquitous regulator of invasive cell spread in both physiological and pathological contexts. In this dataset, we knocked down YAP in two patient-derived GBM primary cell lines (JHGB612 and JHGB651) and performed microarray analysis.
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2025-04-14 | PXD020102 | Pride
Project description:YAP controls cell migration and invasion through a Rho-GTPase switch
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Project description:Aberrant expression of adherens junction (AJ) proteins is frequently observed in human cancers. However, how these factors contribute to tumorigenesis is poorly understood and for some factors such as α‐catenin contradicting data has been described. Systematic analysis of TCGA expression data derived from 23 human tumor types revealed that α‐catenin was significantly reduced in some malignancies (e.g., colon adenocarcinoma), while elevated α‐catenin expression in other entities was associated with poor clinical outcome (e.g., hepatocellular carcinoma; HCC). In HCC cells, α‐catenin was detectable at the membrane as well as cytoplasm where it supported tumor cell proliferation and migration. Additionally, in vivo experiments illustrated moderate oncogenic potential of α‐catenin. To identify functionally relevant binding partners of α‐catenin, BioID combined with mass spectrometry was performed. This led to the identification of cytokinesis regulator centrosomal protein 55 (CEP55) as novel α‐catenin interacting protein in the cytoplasm that was stabilized by α‐catenin. Interestingly, CEP55 was highly expressed in human HCC tissues and its overexpression was transcriptionally controlled by a complex consisting of TEA domain transcription factors (TEADs), forkhead box M1 (FoxM1), and yes-associated protein (YAP). Surprisingly, CEP55 did not significantly affect HCC cell proliferation but supported migration in conjunction with α‐catenin. Together, the enrichment of pro-migratory CEP55 in HCC cells is mediated by two mechanisms: transcriptional activation via the FoxM1/TEAD/YAP as well as the cytoplasmic stabilization through interaction with the AJ protein α‐catenin.
2023-07-20 | PXD039222 | Pride
Project description:Cardiomyocyte (CM) loss after injury results in adverse remodelling and fibrosis, which inevitably lead to heart failure. Neuregulin-ErbB2 and Hippo-Yap signaling pathways are key mediators of CM proliferation and regeneration although the crosstalk between these pathways is unclear. Here, we demonstrate in mice that temporal over-expression (OE) of activated ErbB2 in CMs promotes cardiac regeneration in a heart failure model. Cellularly, OE CMs present an EMT-like regenerative response involving cytoskeletal reprograming, migration, ECM turnover, and displacement. Molecularly, we identified Yap as a critical mediator of ErbB2 signaling. In OE CMs, Yap interacts with nuclear envelope and cytoskeletal components, reflective of the altered mechanic state elicited by ErbB2. Hippo-independent activating phosphorylation on Yap at S352 and S274 were enriched in OE CMs, peaking during metaphase. Viral overexpression of Yap phospho-mutants dampened the proliferative competence of OE CMs. Taken together, we demonstrate a potent ErbB2-mediated Yap mechanosensory signaling involving EMT-like characteristics, resulting in heart regeneration.
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