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Developmental Biology - Cell Adhesion|
Pressure Induces Cells to Get Sticky In the first two weeks of embryo development, 'force' changes cell surface tension — essential in organ formation...
In the first two weeks of embryo development, 'force' changes cell surface tension — essential in organ formation...
These results suggest activation of FGFR is triggered by force induced cell deformation — or shape change. This is a significant step towards addressing the long-standing question of how physical forces influence cell and tissue behaviors.
• Mechanical force induces phosphorylation of cell junction components
• Kinase profile of mechanoresponses revealed rapid activation of basophilic kinases
• The focal adhesion kinase induces PKC activity during mechanoresponse in Xenopus
• Centrifugation force induces MET-like phenotype
Mechanical forces are essential drivers of numerous biological processes, notably during development. Although it is well recognized that cells sense and adapt to mechanical forces, the signal transduction pathways that underlie mechanosensing have remained elusive. Here, we investigate the impact of mechanical centrifugation force on phosphorylation-mediated signaling in Xenopus embryos. By monitoring temporal phosphoproteome and proteome alterations in response to force, we discover and validate elevated phosphorylation on focal adhesion and tight junction components, leading to several mechanistic insights into mechanosensing and tissue restoration. First, we determine changes in kinase activity profiles during mechanoresponse, identifying the activation of basophilic kinases. Pathway interrogation using kinase inhibitor treatment uncovers a crosstalk between the focal adhesion kinase (FAK) and protein kinase C (PKC) in mechanoresponse. Second, we find LIM domain 7 protein (Lmo7) as upregulated upon centrifugation, contributing to mechanoresponse. Third, we discover that mechanical compression force induces a mesenchymal-to-epithelial transition (MET)-like phenotype.
This work was conducted as an international collaboration between Naoto Ueno's group, which includes Noriyuki Kinoshita, Yutaka Hashimoto, Naoko Yasue, Makoto Suzuki, Ileana M. Cristea and Naoto Ueno.
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Eggs of Xenopus Laevis (African clawed frog) are frequently used to study embryonic development because (1) they develop outside of the body and can easily be surgically manipulated or treated with proteins and chemicals that interfere with development (2) embryos become transparent as organogenesis proceeds and are transparent at five days, when organ systems are well defined and subtle morphological defects can be recognized and (3) they have a high tolerance for light exposure.
Information CREDIT National Institutes of Health.