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First published online 14 January 2009
doi: 10.1242/dev.031104

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Glycosphingolipids control the extracellular gradient of the Drosophila EGFR ligand Gurken

¹ Institute of Developmental Biology and Cancer, CNRS UMR 6543, Centre de Biochimie, Université de Nice, Parc Valrose, 06108 Nice Cedex 02, France.
² The Cell Microscopy Centre, Department of Cell Biology, Institute of Biomembranes, University Medical Centre Utrecht, AZU Room H02.313, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
³ Temasek Life Sciences Laboratory, 1 Research Link, Singapore 117604, Republic of Singapore.

^* Author for correspondence (e-mail: pizette{at}unice.fr)

Accepted 2 December 2008

Glycosphingolipids (GSLs) are present in all eukaryotic membranes and are implicated in neuropathologies and tumor progression in humans. Nevertheless, their in vivo functions remain poorly understood in vertebrates, partly owing to redundancy in the enzymes elongating their sugar chains. In Drosophila, a single GSL biosynthetic pathway is present that relies on the activity of the Egghead and Brainiac glycosyltransferases. Mutations in these two enzymes abolish GSL elongation and yield oogenesis defects, providing a unique model system in which to study GSL roles in signaling in vivo. Here, we use egghead and brainiac mutants to show that GSLs are necessary for full activation of the EGFR pathway during oogenesis in a time-dependent manner. In contrast to results from in vitro studies, we find that GSLs are required in cells producing the TGF-like ligand Gurken, but not in EGFR-expressing cells. Strikingly, we find that GSLs are not essential for Gurken trafficking and secretion. However, we characterize for the first time the extracellular Gurken gradient and show that GSLs affect its formation by controlling Gurken planar transport in the extracellular space. This work presents the first in vivo evidence that GSLs act in trans to regulate the EGFR pathway and shows that extracellular EGFR ligand distribution is tightly controlled by GSLs. Our study assigns a novel role for GSLs in morphogen diffusion, possibly through regulation of their conformation.

Key words: Glycosphingolipids, Glycosyltransferases, Egghead, Brainiac, Signaling, Gradient, EGFR, Gurken, Oogenesis, Drosophila

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