naked cuticle encodes an inducible antagonist of Wnt signalling

Wenlin Zeng, Keith A. Wharton, Judith A. Mack, Kevin Wang, Matthew Gadbaw, Kaye Suyama, Peter S. Klein and Matthew P. Scott ()
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Wenlin Zeng: Howard Hughes Medical Institute, Beckman Center B300, Stanford University School of Medicine
Keith A. Wharton: Howard Hughes Medical Institute, Beckman Center B300, Stanford University School of Medicine
Judith A. Mack: Howard Hughes Medical Institute, Beckman Center B300, Stanford University School of Medicine
Kevin Wang: Howard Hughes Medical Institute, Beckman Center B300, Stanford University School of Medicine
Matthew Gadbaw: Howard Hughes Medical Institute, Beckman Center B300, Stanford University School of Medicine
Kaye Suyama: Howard Hughes Medical Institute, Beckman Center B300, Stanford University School of Medicine
Peter S. Klein: Howard Hughes Medical Institute University of Pennsylvania School of Medicine, Clinical Research Building Room 405
Matthew P. Scott: Howard Hughes Medical Institute, Beckman Center B300, Stanford University School of Medicine

Nature, 2000, vol. 403, issue 6771, 789-795

Abstract: Abstract During animal development, cells have to respond appropriately to localized secreted signals. Proper responses to Hedgehog, transforming growth factor-β, epidermal growth factor and fibroblast growth factor/Ras signals require cognate inducible antagonists such as Patched, Dad, Argos and Sprouty1. Wnt signals are crucial in development and neoplasia2. Here we show that naked cuticle (nkd), a Drosophila segment-polarity gene, encodes an inducible antagonist for the Wnt signal Wingless (Wg). In fly embryos and imaginal discs nkd transcription is induced by Wg. In embryos, decreased nkd function has an effect similar to excess Wg; at later stages such a decrease appears to have no effect. Conversely, overproduction of Nkd in Drosophila and misexpression of Nkd in the vertebrate Xenopus laevis result in phenotypes resembling those of loss of Wg/Wnt function. nkd encodes a protein with a single EF hand (a calcium-binding motif) that is most similar to the recoverin family of myristoyl switch proteins. Nkd may therefore link ion fluxes to the regulation of the potency, duration or distribution of Wnt signals. Signal-inducible feedback antagonists such as nkd may limit the effects of Wnt proteins in development and disease.

Date: 2000
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DOI: 10.1038/35001615

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