TY - JOUR
T1 - Wnt/Dkk negative feedback regulates sensory organ size in zebrafish
AU - Wada, Hironori
AU - Ghysen, Alain
AU - Asakawa, Kazuhide
AU - Abe, Gembu
AU - Ishitani, Tohru
AU - Kawakami, Koichi
N1 - Funding Information:
We thank C. Dambly-Chaudière for critical reading of the manuscript. We also thank the anonymous reviewers for many valuable suggestions. The help of M. Iwasaki is gratefully acknowledged. We thank D. Gilmour, M. Itoh, S. Higashijima, H. Okamoto, H. Clevers, T. Piotrowski, and members of the Kawakami lab for fish strains and reagents. This work was supported by the National BioResource Project and funded by the Precursory Research for Embryonic Science and Technology (PRESTO) program of the Japan Science and Technology Agency (to H.W.).
PY - 2013/8/19
Y1 - 2013/8/19
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cub.2013.06.035
DO - 10.1016/j.cub.2013.06.035
M3 - Article
C2 - 23891113
AN - SCOPUS:84882697619
SN - 0960-9822
VL - 23
SP - 1559
EP - 1565
JO - Current Biology
JF - Current Biology
IS - 16
ER -