Affiliation:
1. Division of Developmental Biology, Children's Hospital Medical Center,Cincinnati, OH 45229, USA
Abstract
The signalling molecule Hedgehog (Hh) functions as a morphogen to pattern a field of cells in animal development. Previous studies in Drosophilahave demonstrated that Tout-velu (Ttv), a heparan sulphate polymerase, is required for Hh movement across receiving cells. However, the molecular mechanism of Ttv- mediated Hh movement is poorly defined. We show that Dally and Dally-like (Dly), two Drosophila glypican members of the heparan sulphate proteoglycan (HSPG) family, are the substrates of Ttv and are essential for Hh movement. We show that embryos lacking dly activity exhibit defects in Hh distribution and its subsequent signalling. However,both Dally and Dly are involved and are functionally redundant in Hh movement during wing development. We further demonstrate that Hh movement in its receiving cells is regulated by a cell-to-cell mechanism that is independent of dynamin-mediated endocytosis. We propose that glypicans transfer Hh along the cell membrane to pattern a field of cells.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference77 articles.
1. Amanai, K. and Jiang, J. (2001). Distinct roles of Central missing and Dispatched in sending the Hedgehog signal. Development128,5119-5127.
2. Azpiazu, N., Lawrence, P. A., Vincent, J. P. and Frasch, M.(1996). Segmentation and specification of the Drosophila mesoderm. Genes Dev.10,3183-3194.
3. Baeg, G. H., Lin, X., Khare, N., Baumgartner, S. and Perrimon,N. (2001). Heparan sulfate proteoglycans are critical for the organization of the extracellular distribution of Wingless. Development128,87-94.
4. Bejsovec, A. and Wieschaus, E. (1995). Signaling activities of the Drosophila wingless gene are separately mutable and appear to be transduced at the cell surface. Genetics139,309-320.
5. Belenkaya, T. Y., Han, C., Standley, H. J., Lin, X., Houston,D., Heasman,
J. and Lin, X. (2002). pygopusencodes a nuclear protein essential for Wingless/Wnt signaling. Development129,4089-4101.
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