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Developmental regulation of heparan sulfate proteoglycan synthesis during Drosophila
embryogenesis.
Abstract 2005 MHE Conference
Douglas Bornemann, Sangbin Park and Rahul Warrior.
Department of Developmental and Cell Biology and
Developmental Biology Center, University of California, Irvine, Irvine CA 92617.
Signaling by the BMP4 homolog Decapentaplegic (Dpp) is critical for cell fate specification in a wide
variety of tissues and at several stages during Drosophila development. The most extensively
studied roles for Dpp are in patterning the dorsal region of the early embryo and in regulating cell
proliferation and patterning in the wing imaginal discs. Dpp activity in the wing disc requires heparan
sulfate proteoglycans (HSPGs), and mutations in tout velou (ttv) and sister of tout velou (sotv) that
encode the GAG chain polymerases, impair Dpp signaling.
Ttv and Sotv activities are also essential for Hedgehog (Hh) and Wingless (Wg) signaling, both in
the imaginal discs as well as in the embryo.
Surprisingly however, embryos lacking ttv, sotv and other HSPG biosynthetic enzymes do not show
any alterations in dorsal patterning, a phenotype characteristic of disruptions in the Dpp pathway.
Thus our data suggested that the Dpp pathway, in contrast to the Hh and Wg pathways, appears to
be differentially sensitive to loss of HSPGs at different developmental stages.
In order to understand the basis for these observations we examined the temporal regulation of
GAG chain addition to HSPG core proteins. We found that GAG chain synthesis is under tight
developmental control. Essentially no synthetic activity is detectable in the first three hours of
embryogenesis with a rapid onset between three and four hours following fertilization.The early time
period when the biosynthetic process is inactive correlates precisely with the interval during which a
Dpp/BMP activity gradient is established, while the onset of GAG chain addition coincides with the
time when Hh and Wg signaling first become active in patterning the embryonic epidermis. We find
that the timing of GAG chain addition is not controlled by the regulated expression or activity of a
pathway component. Instead our data argue that GAG chain synthesis is controlled at a
post-transcriptional level through regulated translation of at least one of the GAG chain polymerases.
Interestingly, this regulatory mechanism appears to be phylogenetically conserved, suggesting that
stage or tissue-specific regulation of GAG chain addition could represent an important strategy in
altering the sensitivity of specific signaling pathways at unique stages during development.
embryogenesis.
Abstract 2005 MHE Conference
Douglas Bornemann, Sangbin Park and Rahul Warrior.
Department of Developmental and Cell Biology and
Developmental Biology Center, University of California, Irvine, Irvine CA 92617.
Signaling by the BMP4 homolog Decapentaplegic (Dpp) is critical for cell fate specification in a wide
variety of tissues and at several stages during Drosophila development. The most extensively
studied roles for Dpp are in patterning the dorsal region of the early embryo and in regulating cell
proliferation and patterning in the wing imaginal discs. Dpp activity in the wing disc requires heparan
sulfate proteoglycans (HSPGs), and mutations in tout velou (ttv) and sister of tout velou (sotv) that
encode the GAG chain polymerases, impair Dpp signaling.
Ttv and Sotv activities are also essential for Hedgehog (Hh) and Wingless (Wg) signaling, both in
the imaginal discs as well as in the embryo.
Surprisingly however, embryos lacking ttv, sotv and other HSPG biosynthetic enzymes do not show
any alterations in dorsal patterning, a phenotype characteristic of disruptions in the Dpp pathway.
Thus our data suggested that the Dpp pathway, in contrast to the Hh and Wg pathways, appears to
be differentially sensitive to loss of HSPGs at different developmental stages.
In order to understand the basis for these observations we examined the temporal regulation of
GAG chain addition to HSPG core proteins. We found that GAG chain synthesis is under tight
developmental control. Essentially no synthetic activity is detectable in the first three hours of
embryogenesis with a rapid onset between three and four hours following fertilization.The early time
period when the biosynthetic process is inactive correlates precisely with the interval during which a
Dpp/BMP activity gradient is established, while the onset of GAG chain addition coincides with the
time when Hh and Wg signaling first become active in patterning the embryonic epidermis. We find
that the timing of GAG chain addition is not controlled by the regulated expression or activity of a
pathway component. Instead our data argue that GAG chain synthesis is controlled at a
post-transcriptional level through regulated translation of at least one of the GAG chain polymerases.
Interestingly, this regulatory mechanism appears to be phylogenetically conserved, suggesting that
stage or tissue-specific regulation of GAG chain addition could represent an important strategy in
altering the sensitivity of specific signaling pathways at unique stages during development.
Research authored by Dr. Warrior
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List of Publications via PubMed
(NIH National Library of Medicine)
List of Publications via PubMed
(NIH National Library of Medicine)
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Dr. Warrior's research
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By the Health On the Net Foundation. Click here to verify.# HON Conduct 282463 and is linked on the NIH
National Library of Medicine, Directory of Health Organizations (SIS) website, as well as the link for Patient
Information on The Diseases Database a cross-referenced index of human disease, and the Intute: health & life
sciences a free online service providing access to the very best Web resources for education and research
located in the UK
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