Mechanisms of intercellular Wnt transport

Wnt proteins are secreted glycoproteins that regulate multiple processes crucial to the development and tissue homeostasis of multicellular organisms, including tissue patterning, proliferation, cell fate specification, cell polarity and migration. To elicit these effects, Wnts act as autocrine as well as paracrine signalling molecules between Wnt-producing and Wnt-receiving cells. More than 40 years after the discovery of the Wg/Wnt pathway, it is still unclear how they are transported to fulfil their paracrine signalling functions. Several mechanisms have been proposed to mediate intercellular Wnt transport, including Wnt-binding proteins, lipoproteins, exosomes and cytonemes. In this Review, we describe the evidence for each proposed mechanism, and discuss how they may contribute to Wnt dispersal in tissue-specific and context-dependent manners, to regulate embryonic development precisely and maintain the internal steady state within a defined tissue.