ZFIN ID: ZDB-PUB-130816-2
Wnt/Dkk Negative Feedback Regulates Sensory Organ Size in Zebrafish
Wada, H., Ghysen, A., Asakawa, K., Abe, G., Ishitani, T., and Kawakami, K.
Date: 2013
Source: Current biology : CB   23(16): 1559-65 (Journal)
Registered Authors: Ghysen, Alain, Ishitani, Tohru, Kawakami, Koichi, Wada, Hironori
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified/genetics
  • Animals, Genetically Modified/growth & development
  • Animals, Genetically Modified/physiology
  • Cell Differentiation
  • Cell Proliferation
  • Feedback
  • Gene Expression Regulation, Developmental
  • Intercellular Signaling Peptides and Proteins/genetics*
  • Intercellular Signaling Peptides and Proteins/metabolism
  • Lateral Line System/anatomy & histology
  • Lateral Line System/growth & development*
  • Organ Size
  • Polymerase Chain Reaction
  • Regeneration
  • Wnt Signaling Pathway*
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 23891113 Full text @ Curr. Biol.

Correct organ size must involve a balance between promotion and inhibition of cell proliferation. A mathematical model has been proposed in which an organ is assumed to produce its own growth activator as well as a growth inhibitor, but there is as yet no molecular evidence to support this model. The mechanosensory organs of the fish lateral line system (neuromasts) are composed of a core of sensory hair cells surrounded by nonsensory support cells. Sensory cells are constantly replaced and are regenerated from surrounding nonsensory cells, while each organ retains the same size throughout life. Moreover, neuromasts also bud off new neuromasts, which stop growing when they reach the same size. Here, we show that the size of neuromasts is controlled by a balance between growth-promoting Wnt signaling activity in proliferation-competent cells and Wnt-inhibiting Dkk activity produced by differentiated sensory cells. This negative feedback loop from Dkk (secreted by differentiated cells) on Wnt-dependent cell proliferation (in surrounding cells) also acts during regeneration to achieve size constancy. This study establishes Wnt/Dkk as a novel mechanism to determine the final size of an organ.