A Yap-dependent mechanoregulatory program sustains cell migration for embryo axis assembly

Sousa-Ortega, Ana; Vázquez-Marín, Javier; Sanabria-Reinoso, Estefanía; Corbacho, Jorge; Polvillo, Rocío; Campoy-Lopez, Alejandro; Buono, Lorena; Loosli, Felix; Almuedo-Castillo, María; Martı́nez-Morales, Juan Ramón

doi:10.1038/s41467-023-38482-w

Cited by 5 publications

(4 citation statements)

References 82 publications

(142 reference statements)

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“… 88 Furthermore, several studies showed that YAP signaling is required to maintain cellular tension in various cells. 89–92 Interestingly, a recent study found that verteporfin, a YAP inhibitor, 93,94 reduced survivin expression in gastric cancer cells. 95 Thus, YAP might represent a regulator of survivin to modulate cellular tension.…”

Section: Discussionmentioning

confidence: 99%

Survivin regulates intracellular stiffness and extracellular matrix production in vascular smooth muscle cells

Krajnik,

Nimmer,

Brazzo

et al. 2023

APL Bioengineering

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Vascular dysfunction is a common cause of cardiovascular diseases characterized by the narrowing and stiffening of arteries, such as atherosclerosis, restenosis, and hypertension. Arterial narrowing results from the aberrant proliferation of vascular smooth muscle cells (VSMCs) and their increased synthesis and deposition of extracellular matrix (ECM) proteins. These, in turn, are modulated by arterial stiffness, but the mechanism for this is not fully understood. We found that survivin is an important regulator of stiffness-mediated ECM synthesis and intracellular stiffness in VSMCs. Whole-transcriptome analysis and cell culture experiments showed that survivin expression is upregulated in injured femoral arteries in mice and in human VSMCs cultured on stiff fibronectin-coated hydrogels. Suppressed expression of survivin in human VSMCs significantly decreased the stiffness-mediated expression of ECM components related to arterial stiffening, such as collagen-I, fibronectin, and lysyl oxidase. By contrast, expression of these ECM proteins was rescued by ectopic expression of survivin in human VSMCs cultured on soft hydrogels. Interestingly, atomic force microscopy analysis showed that suppressed or ectopic expression of survivin decreases or increases intracellular stiffness, respectively. Furthermore, we observed that inhibiting Rac and Rho reduces survivin expression, elucidating a mechanical pathway connecting intracellular tension, mediated by Rac and Rho, to survivin induction. Finally, we found that survivin inhibition decreases FAK phosphorylation, indicating that survivin-dependent intracellular tension feeds back to maintain signaling through FAK. These findings suggest a novel mechanism by which survivin potentially modulates arterial stiffness.

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Section: Discussionmentioning

confidence: 99%

Survivin regulates intracellular stiffness and extracellular matrix production in vascular smooth muscle cells

Krajnik,

Nimmer,

Brazzo

et al. 2023

APL Bioengineering

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“…This impairment would decrease yap-dependent mechano-transduction, which, in turn, could affect the contraction of the actomyosin network, delaying epiboly progression ( Figure 7 ). In support of this model, the yap mechano-regulatory program seems to be essential for sustaining intracellular tension during gastrulation, that, in turn, controls the assembly of the embryonic A-P axis ( Sousa-Ortega et al, 2023 ). Our simplified model does not take into account other and yet undetermined factors that contribute to this process.…”

Section: Discussionmentioning

confidence: 93%

Maternal vgll4a regulates zebrafish epiboly through Yap1 activity

Camacho-Macorra,

Tabanera,

Sánchez-Bustamante

et al. 2024

Front. Cell Dev. Biol.

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Gastrulation in zebrafish embryos commences with the morphogenetic rearrangement of blastodermal cells, which undergo a coordinated spreading from the animal pole to wrap around the egg at the vegetal pole. This rearrangement, known as epiboly, relies on the orchestrated activity of maternal transcripts present in the egg, compensating for the gradual activation of the zygotic genome. Epiboly involves the mechano-transducer activity of yap1 but what are the regulators of yap1 activity and whether these are maternally or zygotically derived remain elusive. Our study reveals the crucial role of maternal vgll4a, a proposed Yap1 competitor, during zebrafish epiboly. In embryos lacking maternal/zygotic vgll4a (MZvgll4a), the progression of epiboly and blastopore closure is delayed. This delay is associated with the ruffled appearance of the sliding epithelial cells, decreased expression of yap1-downstream targets and transient impairment of the actomyosin ring at the syncytial layer. Our study also shows that, rather than competing with yap1, vgll4a modulates the levels of the E-cadherin/β-catenin adhesion complex at the blastomeres’ plasma membrane and hence their actin cortex distribution. Taking these results together, we propose that maternal vgll4a acts at epiboly initiation upstream of yap1 and the E-cadherin/β-catenin adhesion complex, contributing to a proper balance between tissue tension/cohesion and contractility, thereby promoting a timely epiboly progression.

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“…YAP proteins, renowned transcriptional regulators, exhibit nuclear translocation in response to mechanical stimulation, displaying activity in the spreading of cells. , This mechanosensing capability relies on actomyosin contractility, actin capping, severing proteins, and coupling between the ECM and the nuclear envelope. , …”

Section: Intracellular Signaling Pathways Mediating Mechanoregulationmentioning

confidence: 99%

The Plasma Membrane and Mechanoregulation in Cells

Mukhopadhyay,

Mandal,

Chakraborty

et al. 2024

ACS Omega

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Cells inhabit a mechanical microenvironment that they continuously sense and adapt to. The plasma membrane (PM), serving as the boundary of the cell, plays a pivotal role in this process of adaptation. In this Review, we begin by examining well-studied processes where mechanoregulation proves significant. Specifically, we highlight examples from the immune system and stem cells, besides discussing processes involving fibroblasts and other cell types. Subsequently, we discuss the common molecular players that facilitate the sensing of the mechanical signal and transform it into a chemical response covering integrins YAP/TAZ and Piezo. We then review how this understanding of molecular elements is leveraged in drug discovery and tissue engineering alongside a discussion of the methodologies used to measure mechanical properties. Focusing on the processes of endocytosis, we discuss how cells may respond to altered membrane mechanics using endo- and exocytosis. Through the process of depleting/adding the membrane area, these could also impact membrane mechanics. We compare pathways from studies illustrating the involvement of endocytosis in mechanoregulation, including clathrin-mediated endocytosis (CME) and the CLIC/GEEC (CG) pathway as central examples. Lastly, we review studies on cell–cell fusion during myogenesis, the mechanical integrity of muscle fibers, and the reported and anticipated roles of various molecular players and processes like endocytosis, thereby emphasizing the significance of mechanoregulation at the PM.

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A Yap-dependent mechanoregulatory program sustains cell migration for embryo axis assembly

Cited by 5 publications

References 82 publications

Survivin regulates intracellular stiffness and extracellular matrix production in vascular smooth muscle cells

Survivin regulates intracellular stiffness and extracellular matrix production in vascular smooth muscle cells

Maternal vgll4a regulates zebrafish epiboly through Yap1 activity

The Plasma Membrane and Mechanoregulation in Cells

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