title: Wnt/Dkk negative feedback regulates sensory organ size in zebrafish.
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.
authors.affiliation: PRESTO, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 322-0012, Japan. hiwada@nig.ac.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Wada
authors.forename: Alain
authors.initials: A
authors.lastname: Ghysen
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Asakawa
authors.forename: Gembu
authors.initials: G
authors.lastname: Abe
authors.forename: Tohru
authors.initials: T
authors.lastname: Ishitani
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000254:growth & development / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D005246:Feedback; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D053403:Lateral Line System / Q000033:anatomy & histology / Q000254:growth & development*; D009929:Organ Size; D016133:Polymerase Chain Reaction; D012038:Regeneration; D060449:Wnt Signaling Pathway; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D029961:Zebrafish Proteins; C501128:dkk1b protein, zebrafish