Persistent cell motility requires transcriptional feedback of cytoskeletal – focal adhesion equilibrium by YAP/TAZ

Devon E Mason, James H Dawahare, Trung Dung Nguyen, Yang Lin, Sherry L. Voytik-Harbin, Pinar Zorlutuna, Mervin E Yoder, Joel D Boerckel

Preprint posted on 15 February 2018

Keep YAP/TAZ activity and carry on. YAP/TAZ reads the mechanical environment and feeds back onto the cytoskeletal machinery to allow for persistent cell migration.

Selected by Carla Mulas

Categories: cell biology


Cell migration requires the coordination of actomyosin contraction, F-actin processing, and focal adhesion remodeling. The environment plays a key role, as cells interpret both chemical and mechanical signals to alter their behavior. These signals interface with the machinery that regulates tension, actin processing and focal adhesion turnover, and can also alter gene expression. But is there a role for transcription in directing cell migration? Can the environment-mediated changes in transcription influence cell behavior? These are the questions under debate in this preprint. Mason and colleagues uncover a feedback mechanism by which the mechanosensitive YAP/TAZ transcription factors affect cell migration. To model this process, they use endothelial colony forming cells (ECFCs), circulating endothelial progenitors that play a role in forming new vasculature during wound repair and development.


What are the key findings?

By using ECFC cells, the authors confirm that YAP/TAZ are mechanosensitive – they are capable of sensing both matrix stiffness and cell density, and become nuclear (and therefore active) in stiffer and less crowded environments.

Surprisingly, chemical inhibition of transcription or depletion of YAP/TAZ reduces the speed and directionality of migration. The effect is not due to reduced expression of cytoskeletal components, which generally have half-lives greater than the experimental time window and are found in excess, nor failure to initiate cell polarisation.

Instead, YAP/TAZ-depleted cells show increased anchorage to the matrix, and increased cytoskeletal prestress: a larger amount of actin stress fibers, greater number of focal adhesions and focal adhesion length, and greater amount of phosphorylated myosin light chain. This shows that YAP/TAZ activity is essential for motility in ECFC cells.

How is it that YAP/TAZ transcriptional activity alters cell behavior, if it is not related to cytoskeletal gene expression? Upon YAP/TAZ depletion, the authors identify a rapid increase in expression of NUAK2, a kinase which deactivates the myosin light chain phosphatase and therefore reduces actomyosin contractility. Abrogating NUAK2 expression in YAP/TAZ-depleted cells mostly rescues migration, focal adhesion size and the amount of stress fibers.

Does this apply in a more complex 3D system, when the endothelial progenitor cells have to organize and form new vasculature, and sense their environment? The authors’ data suggest that it does: when YAP/TAZ activity or levels are reduced, either in cells transplanted in vivo, or in aorta explant cultures, vascular sprouting was also reduced.


Why this is cool

As a non-cell mechanics person (I work on cell fate decisions in stem cells), I found this a really interesting study. It provides a mechanism by which cells can rapidly sense and respond to the environment, either as individuals or during collective cell migration.

YAP/TAZ have also been shown to coordinate cell fate decisions in different systems. For example, modulation of YAP/TAZ causes defects in branching morphogenesis in the developing lung and kidney1,2. It would be interesting to see whether in such systems YAP/TAZ were able to coordinate morphogenesis with cell fate specification. Furthermore, could the YAP/TAZ feedback system on the cytoskeleton also allow cells to collectively sense a preferred path of migration within matrices with varying stiffness?



  1. Reginensi, A., Enderle, L., Gregorieff, A., Johnson, R. L., Wrana, J. L. & McNeill, H. A critical role for NF2 and the Hippo pathway in branching morphogenesis. Nature Communications 7, 12309 (2016).
  2. Lin, C., Yao, E., Zhang, K., Jiang, X., Croll, S., Thompson-Peer, K. & Chuang, P.-T. YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis. eLife 6, 14665 (2017).


Posted on: 27 February 2018 , updated on: 6 March 2018

Read preprint (No Ratings Yet)

Author's response

Devon Mason & Joel Boerckel shared

Whether regulated transcription is needed for migration has been a long-standing question. We were surprised to find that preventing either transcription or translation caused motility arrest, not because the cells “run out of gas,” so to speak, but rather because they lose the ability to put a break on actin tension and adhesion maturation. We were particularly excited to find that this is regulated by a feedback loop in which cytoskeletal dynamics induce transcriptional regulators that in turn modulate the cytoskeleton. Determining the role of this cytoskeletal feedback system in neovascularization in vivo is certainly an interesting follow-up question we’re chasing.

We very much appreciate the implications you raise. Our laboratory is broadly interested in the mechanobiology of morphogenesis and regeneration, and we are excited to test the role of this feedback mechanism in these contexts. For example, we recently found that YAP and TAZ combinatorially determine the shape and constitution of bone matrix during development.1 Interestingly, similar to our observations here, we found that YAP and TAZ can partially compensate for one another, but also exhibit differential potency. We are very interested to understand the mechanisms that provide this contextual specificity and to determine the extent to which this cytoskeletal feedback influences cell fate decisions.

Your question about durotaxis an excellent one: how do cells migrate from regions of low to high matrix rigidity without getting stuck? Is mechanotransduction merely a one-way street, in which mechanical cues induce transcription factor activation, gene expression, and cell fate decisions linearly, or could these events require transcriptional feedback? We are anxious to find out!

  1. Kegelman CD, Mason DE, Dawahare JH, Horan DJ, Vigil GD, Howard SS, Robling AG, Bellido TM, Boerckel JD. Skeletal cell YAP and TAZ combinatorially promote bone development. FASEB J; 2018 Jan 10;fj.201700872R.

Have your say

Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

preLists in the cell biology category:


The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!


List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.


List by Alex Eve

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020


List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.


List by Ana Dorrego-Rivas

BioMalPar XVI: Biology and Pathology of the Malaria Parasite

[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria


List by Dey Lab, Samantha Seah


Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.


List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20


List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.


List by Paul Gerald L. Sanchez and Stefano Vianello

ECFG15 – Fungal biology

Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome


List by Hiral Shah

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)


List by Madhuja Samaddar et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019


List by Dey Lab


Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.


List by Sandra Malmgren Hill

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.


List by Rob Hynds

Cellular metabolism

A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.


List by Pablo Ranea Robles

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019


List by Dey Lab


This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.


List by Sandra Franco Iborra

Biophysical Society Annual Meeting 2019

Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA


List by Joseph Jose Thottacherry

ASCB/EMBO Annual Meeting 2018

This list relates to preprints that were discussed at the recent ASCB conference.


List by Dey Lab, Amanda Haage