National Institute for Basic Biology and Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki, Japan; The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Japan; Japan Science and Technology Agency (JST), PRESTO, Kawaguchi, Japan; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan
Kenichi Nakazato
Theoretical Biology Laboratory, RIKEN, Wako, Japan
Cellular Informatics Laboratory, RIKEN, Wako, Japan; ASAN Institute for Life Sciences, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Takafumi Ikeda
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan
Yasushi Sako
Cellular Informatics Laboratory, RIKEN, Wako, Japan
Atsushi Mochizuki
Theoretical Biology Laboratory, RIKEN, Wako, Japan; Laboratory of Mathematical Biology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
Masanori Taira
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan; Department of Biological Sciences, Faculty of Science and Engineering, Chuo University, Tokyo, Japan
National Institute for Basic Biology and Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki, Japan; The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Japan
The mechanism of intercellular transport of Wnt ligands is still a matter of debate. To better understand this issue, we examined the distribution and dynamics of Wnt8 in Xenopus embryos. While Venus-tagged Wnt8 was found on the surfaces of cells close to Wnt-producing cells, we also detected its dispersal over distances of 15 cell diameters. A combination of fluorescence correlation spectroscopy and quantitative imaging suggested that only a small proportion of Wnt8 ligands diffuses freely, whereas most Wnt8 molecules are bound to cell surfaces. Fluorescence decay after photoconversion showed that Wnt8 ligands bound on cell surfaces decrease exponentially, suggesting a dynamic exchange of bound forms of Wnt ligands. Mathematical modeling based on this exchange recapitulates a graded distribution of bound, but not free, Wnt ligands. Based on these results, we propose that Wnt distribution in tissues is controlled by a dynamic exchange of its abundant bound and rare free populations.
