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Updated: May 9, 2026
Confocal Microscope-Based Laser Ablation and Regeneration Assay in Zebrafish Interneuromast Cells
Published on: May 20, 2020
Wnt/Dkk negative feedback regulates sensory organ size in zebrafish
Hironori Wada1, Alain Ghysen, Kazuhide Asakawa
1PRESTO, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 322-0012, Japan. hiwada@nig.ac.jp
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.
Insights
Organ size is regulated by a balance between growth promotion and inhibition. This study reveals Wnt/Dkk signaling in fish neuromasts controls organ size and regeneration, establishing a novel mechanism for size constancy.
Area of Science:
- Developmental Biology
- Cell Biology
- Organogenesis
Background:
- Organ size is determined by the balance between cell proliferation and inhibition.
- Previous models proposed growth activators and inhibitors, but lacked molecular evidence.
- Fish lateral line neuromasts maintain constant size despite cell turnover and budding.
Purpose of the Study:
- To investigate the molecular mechanisms controlling organ size in fish neuromasts.
- To identify signaling pathways involved in maintaining size constancy during regeneration.
- To establish a novel mechanism for organ size determination.
Main Methods:
- Analysis of Wnt signaling pathway activity in fish neuromast development and regeneration.
- Investigating the role of Dkk as a Wnt inhibitor.
- Utilizing genetic and molecular techniques to study cell proliferation and differentiation.
Main Results:
- Wnt signaling promotes cell proliferation in proliferation-competent cells within neuromasts.
- Dkk, produced by differentiated sensory cells, inhibits Wnt signaling.
- A negative feedback loop between Wnt and Dkk controls proliferation and ensures size constancy during regeneration.
Conclusions:
- Wnt/Dkk signaling acts as a novel mechanism to regulate organ size.
- This feedback loop is crucial for maintaining size constancy in neuromasts.
- The findings provide molecular insight into organogenesis and regeneration.
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