Wnt/Dkk negative feedback regulates sensory organ size in zebrafish

Hironori Wada, Alain Ghysen, Kazuhide Asakawa, Gembu Abe, Tohru Ishitani, Koichi Kawakami

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36 Citations (Scopus)

Abstract

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 [1], but there is as yet no molecular evidence to support this model [2]. 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 [3], 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 [4, 5]. 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.

Original languageEnglish
Pages (from-to)1559-1565
Number of pages7
JournalCurrent Biology
Volume23
Issue number16
DOIs
Publication statusPublished - Aug 19 2013

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Wada, H., Ghysen, A., Asakawa, K., Abe, G., Ishitani, T., & Kawakami, K. (2013). Wnt/Dkk negative feedback regulates sensory organ size in zebrafish. Current Biology, 23(16), 1559-1565. https://doi.org/10.1016/j.cub.2013.06.035