Frizzled receptor-mediated mechanisms of Wingless signaling in developing Drosophila wing epithelium
Authors: Swapnil Hingole; Varun Chaudhary
Affiliation: Indian Institute of Science Education and Research (IISER) Bhopal, India
Keywords: g. wing disc; g. wing disc
Wnts are evolutionarily conserved lipid-modified glycoproteins. Secreted Wnts can travel up to several cell distances over receiving cells and generate a response in a concentration-dependent manner. Their ability to regulate the growth and differentially pattern the tissue makes them crucial for embryonic development and adult tissue homeostasis. Wnts can act directly at a short-range and long-range, which is best studied in the developing Drosophila wing imaginal disc. Wingless (Wg, Wnt1 homolog in Drosophila) is secreted from narrow stripes of cells along the dorsoventral boundary of the wing disc and activates both short and long-range signaling. However, the mechanisms of long-range gradient signaling are sparsely understood and highly debated. Replacing endogenous Wg with membrane-tethered Wg was able to maintain long-range target gene expression even in the absence of gradient in wing disc and developed a normally patterned wing. Moreover, studies have also demonstrated that long-range target gene expression can be maintained in a ligand-independent manner.
Our findings show that Frizzled 2 (Fz2), a receptor of Wg, maintains target gene expression beyond the reach of Wg protein in a ligand-independent manner. Fz2 acts redundantly with Fz1 to activate Wg-dependent canonical signaling. However, we found that the maintenance of signaling is a novel non-redundant function of Fz2. This makes Fz2 highly important for the survival and patterning of cells in the absence of the proper Wg gradient. We also show that the Fz2 mediated maintenance of signaling is not dependent on other Wnt ligands. Together these findings and the elevated Fz2 levels in the absence of Wg protein suggest that receptor oligomerization and internalization could be possible mechanisms behind the maintenance of signaling. Thus the combinatorial effect of direct Wg dependent signaling and Fz2 mediated ligand-independent maintenance provides robustness to the developing wing epithelium experiencing varying concentrations of Wg ligand.