Dickkopf controls neuromast size during lateral line development

Hironori Wada1,, and Koichi Kawakami2

2)National Institute of Genetics; SOKENDAI

Size is important for proper functions of an organ during animal development. However, little is known about mechanisms that coordinate relative organ size with overall body size. The lateral line system comprises a large number of mechanosensory organs, the neuromasts, distributed over the body surface of fish. In the previous study, we demonstrated that the embryonic neuromast gives rise to a series of accessory neuromasts by a serial budding process. The budding process increases number of the organs as fish grow, while each neuromast maintains a constant size independently of body size. In this study, to understand the molecular basis for the neuromast size control, we searched for genes that are differentially expressed in forming neuromasts of zebrafish. We show that Wnt inhibitory factors, Dickkopf family genes (Dkks), are strongly expressed in hair cells and their precursors in differentiating neuromasts. We also show that the Wnt-signaling downstream activities are detectable only in the budding cells. To reveal roles of Dkks during neuromast development, we performed knock-down of Dkk gene functions by antisense morpholino oligonucleotides (MO). In the absence of Dkk gene functions, neuromasts are significantly larger than that in control embryos. Next, we overexpressed Dkk in the proximity of developing neuromasts by using a Gal4-UAS system. In the Dkk-overexpressing embryos, neuromasts become smaller than that in control embryos. Importantly, proportion of cell types in each neuromast is not affected in loss- or gain-of-function experiments, showing that Dkk controls proliferation of neuromast without affecting its patterning. We suggest a novel organ intrinsic growth mechanism to control organ size.