Role of cytonemes in Wnt transport

Abstract

Wnt signaling regulates a broad variety of processes during embryonic development and disease. A hallmark of the Wnt signaling pathway is the formation of concentration gradients by Wnt proteins across responsive tissues, which determines cell fate in invertebrates and vertebrates. To fulfill its paracrine function, trafficking of the Wnt morphogen from an origin cell to a recipient cell must be tightly regulated. A variety of models have been proposed to explain the extracellular transport of these lipid-modified signaling proteins in the aqueous extracellular space; however, there is still considerable debate with regard to which mechanisms allow the precise distribution of ligand in order to generate a morphogenetic gradient within growing tissue. Recent evidence suggests that Wnt proteins are distributed along signaling filopodia during vertebrate and invertebrate embryogenesis. Cytoneme-mediated transport has profound impact on our understanding of how Wnt signaling propagates through tissues and allows the formation of a precise ligand distribution in the recipient tissue during embryonic growth. In this Commentary, we review extracellular trafficking mechanisms for Wnt proteins and discuss the growing evidence of cytoneme-based Wnt distribution in development and stem cell biology. We will also discuss their implication for Wnt signaling in the formation of the Wnt morphogenetic gradient during tissue patterning.

Butterfly eyespot organiser: in vivo imaging of the prospective focal cells in pupal wing tissues

“…Cell clustering through horizontal processes may be a general feature of butterfly wing epithelium, which would contribute to cellular communication. In Drosophila , cytonemes play a critical role in distributing morphogenic signal proteins3536373839. It is possible that the horizontal processes that were observed in this study function as cytonemes to distribute morphogenic signal proteins.…”

Exosomes in developmental signalling

“…One possibility is that WNT and HH may not need to diffuse in order to act at a long range. Indeed, it has been suggested that these proteins could remain tethered to specialised signalling filopodia called cytonemes, which extend to distant cells (Bischoff et al, 2013;Hsiung et al, 2005;Ramirez-Weber and Kornberg, 1999;Stanganello and Scholpp, 2016). However, there is as yet no specific means of preventing cytoneme formation, precluding a direct test of this model.…”

Visualizing Wnt secretion from Endoplasmic Reticulum to Filopodia

“…Wnts bind to cell surface receptors to activate diverse signaling pathways, the beststudied of which leads to the stabilization of β -catenin and the activation of target gene expression. Less is known about how Wnts travel from one cell to engage receptors on neighboring cells (Yamamoto et al 2013;Yu & Virshup 2014;Stanganello & Scholpp 2016).…”

“…Several contrasting models have been proposed to explain how Wnts travel from the producing cell to the receiving cell (reviewed in Stanganello & Scholpp 2016). All models 50 must explain how the hydrophobic palmitoleate moiety on Wnt is protected from an aqueous environment.…”