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First published online 7 January 2004
doi: 10.1242/dev.00958

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Drosophila glypicans control the cell-to-cell movement of Hedgehog by a dynamin-independent process

Chun Han, Tatyana Y. Belenkaya^*, Bei Wang^* and Xinhua Lin

Division of Developmental Biology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA

Author for correspondence (e-mail: linyby{at}chmcc.org)

Accepted 30 October 2003

The signalling molecule Hedgehog (Hh) functions as a morphogen to pattern a field of cells in animal development. Previous studies in Drosophila have 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.

Key words: Hedgehog, Heparan sulphate proteoglycans, Glypican, Dally; Dally-like, Drosophila, Morphogen gradient formation, Signaling

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