Knkco-down of wnk reduces wing size
The Jenny Lab

Department of
Developmental and Molecular Biology at

Albert Einstein

Science at the Heart of Medicine


Wnt/Wingless (Wg) growth factors commonly signal through either the canonical Wnt (Wg)-Frizzled (Fz)/β-catenin pathway or through non-canonical Wnt pathways such as the Wnt/Fz-planar cellular polarity (PCP) pathway, regulating the polarization of cells within the pane of the epithelium. These two pathways are highly conserved between humans, mice, fish and flies.

Canonical Wnt/β-catenin signaling is essential for many aspects of development. For example in vertebrates, it controls the specification of the dorsal-ventral (D-V) embryonic axis, cell proliferation in many tissues, maintenance of stem cells, and vascularization. In addition, aberrant canonical Wnt signaling in humans causes cancer. In collaboration with other labs, we performed a systematic RNAi screen in Drosophila S2 cells to identify kinases and phosphatases that regulate Wnt signaling using phosphorylation of the adapter protein Dishevelled as readout.

We identified Wnk (With No Lysine [K]) kinase as a novel regulator of peak canonical Wnt signaling in Drosophila. Wnk kinases are well known for their role in the regulation of ion homeostasis in the kidney, where their lack causes hypertension (Gordon syndrome). Importantly, this novel function of Wnk in the regulation of Wnt signaling appears to be conserved in human cells.

Wnk knock-down:

RNAi mwh

Compared to wild-type (top), in vivo knock-down of wnk in the posterior compartment of a wing disc (marked by the absence of Ci stain in blue; bottom) leads to a reduction of the expression of the direct Wnt target Sens (green) without affecting Wg expression (red).