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

Development. 2015 Aug 15;142(16):2752-63. doi: 10.1242/dev.119701. Epub 2015 Jul 24.

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.

Keywords: Cell density; F-actin; Fin regeneration; Hippo/Yap; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animal Fins / metabolism
  • Animal Fins / physiology*
  • 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 / physiology*
  • Zebrafish Proteins / metabolism*

Substances

  • Actins
  • Oligonucleotides, Antisense
  • Trans-Activators
  • YAP-Signaling Proteins
  • Yes-associated protein (yap), zebrafish
  • Zebrafish Proteins