Wingless (Wg) is a morphogen required for the patterning of many Drosophila tissues. Several lines of evidence implicate heparan sulfate-modified proteoglycans (HSPGs) such as Dally-like protein (Dlp) in the control of Wg distribution and signaling. We show that dlp is required to limit Wg levels in the matrix, contrary to the expectation from overexpression studies. dlp mutants show ectopic activation of Wg signaling at the presumptive wing margin and a local increase in extracellular Wg levels. dlp somatic cell clones disrupt the gradient of extracellular Wg, producing ectopic activation of high threshold Wg targets but reducing the expression of lower threshold Wg targets where Wg is limiting. Notum encodes a secreted protein that also limits Wg distribution, and genetic interaction studies show that dlp and Notum cooperate to restrict Wg signaling. These findings suggest that modification of an HSPG by a secreted hydrolase can control morphogen levels in the matrix.
Bibliographical noteFunding Information:
We thank W. Ross Waldrip, Sarah Knox, and Xiao-bo Chen for their contributions to the genetic characterization of dlp mutants, J. Sekelsky for providing dlp alleles, and S. Baumgartner for providing anti-Dlp antibody prior to publication. We are indebted to R. Nusse, S. Cohen, T. Neufeld, and H. Nakato for reagents, critical reading of the manuscript, and sharing of results prior to publication, as well as the Developmental Studies Hybridoma Bank at the University of Iowa for antibodies. This work was supported by NIH grant RO1 GM54832 to S.B.S., the March of Dimes, salary support for J.M.R. from NIH GM054832-08 to Arthur Lander, and the Harrison Endowment Fund to S.B.S.
Copyright 2008 Elsevier B.V., All rights reserved.