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A translational block to HSPG synthesis permits BMP signaling in the early Drosophila embryo
Douglas J. Bornemann1,
Sopheap Phin1, and
1 Developmental and Cell Biology and Developmental Biology Center, University of
California Irvine, Irvine, CA, USA. 2 Department of Developmental Biology, Stanford University School of Medicine,
Stanford, CA, USA.
Author for correspondence (e-mail:
Accepted for publication 6 January 2008.
Heparan sulfate proteoglycans (HSPGs) are extracellular macromolecules
foundon virtually every cell type in eumetazoans. HSPGs are composedof a
core protein covalently linked to glycosaminoglycan (GAG)sugar chains that
bind and modulate the signaling efficiencyof many ligands, including Hedgehog
(Hh), Wingless (Wg) andBone morphogenetic proteins (BMPs). Here, we show
that, in Drosophila,loss of HSPGs differentially affects embryonic
Hh, Wg and BMPsignaling. We find that a stage-specific block to GAG synthesis
preventsHSPG expression during establishment of the BMP activity gradient
thatis crucial for dorsal embryonic patterning. Subsequently, GAGsynthesis
is initiated coincident with the onset of Hh and Wgsignaling which require
HSPGs. This temporal regulation is achievedby the translational control of
HSPG synthetic enzymes throughinternal ribosome entry sites (IRESs).
IRES-like features areconserved in GAG enzyme transcripts from diverse
organisms,suggesting that this represents a novel evolutionarily conserved
mechanismfor regulating GAG synthesis and modulating growth factor