2013/07/26

Wnt/Dkk negative feedback regulates sensory organ size in zebrafish

Division of Molecular and Developmental Biology • Kawakami Group

Wnt/Dkk negative feedback regulates sensory organ size in zebrafish.
H. Wada, A. Ghysen, K. Asakawa, G. Abe, T. Ishitani, K. Kawakami.
Current Biology, 23 (16), p1559–1565, DOI: 10.1016/j.cub.2013.06.035

Correct organ size must involve a balance between promotion and inhibition of cell proliferation. A mathematical model has been proposed, where an organ is assumed to produce its own growth activator, as well as a growth inhibitor. But, there is 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 non-sensory support cells. Sensory cells are constantly replaced, and are regenerated by surrounding non-sensory cell, 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. In this study, 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.

This study was funded by the PRESTO of the Japan Science and Technology Agency.

A) Schematic drawing of a neuromast.
(B) Schematic representation of Wnt signaling and of its inhibition by Dkk signaling.
(C) Wnt reporter activity (green) gradually subsides as hair cells (red) are formed.
(D) Dkk2 expression coincides with neuromast maturation.


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