Control of tissue growth by Yap relies on cell density and F-actin in zebrafish fin regeneration

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Rita Mateus - , CEDOC, NOVA University Lisbon (Author)
  • Raquel Lourenço - , NOVA University Lisbon (Author)
  • Yi Fang - , National Institute of Environmental Health Sciences (Author)
  • Gonçalo Brito - , Instituto de Medicina Molecular - João Lobo Antunes (Author)
  • Ana Farinho - , NOVA University Lisbon (Author)
  • Fábio Valério - , NOVA University Lisbon (Author)
  • Antonio Jacinto - , NOVA University Lisbon (Author)

Abstract

Caudal fin regeneration is characterized by a proliferation boost in the mesenchymal blastema that is controlled precisely in time and space. This allows a gradual and robust restoration of original fin size. However, how this is established and regulated is not well understood. Here, we report that Yap, the Hippo pathway effector, is a chief player in this process: functionally manipulating Yap during regeneration dramatically affects cell proliferation and expression of key signaling pathways, impacting regenerative growth. The intracellular location of Yap is tightly associated with different cell densities along the blastema proximal-distal axis, which correlate with alterations in cell morphology, cytoskeleton and cell-cell contacts in a gradient-like manner. Importantly, Yap inactivation occurs in high cell density areas, conditional to F-actin distribution and polymerization. We propose that Yap is essential for fin regeneration and that its function is dependent on mechanical tension, conferred by a balancing act of cell density and cytoskeleton activity.

Details

Original languageEnglish
Pages (from-to)2752-63
Number of pages12
JournalDevelopment (Cambridge, England)
Volume142
Issue number16
Publication statusPublished - 15 Aug 2015
Peer-reviewedYes
Externally publishedYes

External IDs

PubMedCentral PMC6514408
ORCID /0000-0002-6023-3880/work/153110496
Scopus 84939600217

Keywords

Keywords

  • Actins/metabolism, Animal Fins/metabolism, Animals, Cell Count, Cell Proliferation/physiology, Cytoskeleton/physiology, Image Processing, Computer-Assisted, In Situ Hybridization, Microscopy, Fluorescence, Oligonucleotides, Antisense/genetics, Real-Time Polymerase Chain Reaction, Regeneration/physiology, Signal Transduction/physiology, Trans-Activators/metabolism, YAP-Signaling Proteins, Zebrafish/metabolism, Zebrafish Proteins/metabolism