A Wingful of Wingless

Science's STKE  21 May 2002:
Vol. 2002, Issue 133, pp. tw179-TW179
DOI: 10.1126/stke.2002.133.tw179

The Wnt protein encoded by the Drosophila wingless gene has critical roles in pattern formation during embryonic development and also in later development of the adult appendages. In embryonic development, the wingless (Wg) signal promotes expression of the product of the naked cuticle gene, Nkd, which functions as an intracellular inhibitor of wingless (Wg) signaling, thus providing a critical negative feedback loop. Given that Nkd appears to have no effect during development of the adult tissues, Gerlitz and Basler screened for additional genes whose expression pattern was consistent with function as a feedback inhibitor for Wg signaling. They isolated a new gene they call wingful. The Wf protein is a secreted protein with sequence similarity to hydrolases, indicating that it might function extracellularly to cleave a signaling molecule. Loss of function of Wf enhanced Wg signaling, whereas gain of Wf function inhibited Wf signaling. But Wf acted on development of the adult tissues, not the embryonic ones responsive to Nkd. The authors note that the two inhibitors of Wg signaling appear beautifully adapted to their respective roles. In early development, where Wg signals at short range, the Nkd protein inhibits intracellular signals whereas in later development of adult tissues, where Wg signaling occurs over a longer range, the extracellular Wf inhibitor comes into play, presumably assuring just the right shape and range of the Wg morphogen gradient.

O. Gerlitz, K. Basler, Wingful, an extracellular feedback inhibitor of wingless. Genes Dev. 16, 1055-1059 (2002). [Abstract] [Full Text]