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

0303 health sciences Cell Count YAP-Signaling Proteins Oligonucleotides, Antisense Zebrafish Proteins Real-Time Polymerase Chain Reaction Actins 03 medical and health sciences Microscopy, Fluorescence Animal Fins Image Processing, Computer-Assisted Trans-Activators Animals Regeneration Cytoskeleton In Situ Hybridization Zebrafish Cell Proliferation Signal Transduction
DOI: 10.1242/jcs.178871 Publication Date: 2015-09-01T14:41:09Z
ABSTRACT
Caudal fin regeneration is characterized by a proliferation boost in the mesenchymal blastema 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 its function is dependent on mechanical tension, conferred by a balancing act of cell density and cytoskeleton activity.
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