Research article summary (published 4 Feb 2008):

A translational block to HSPG synthesis permits BMP signaling in the early Drosophila embryo.

Full Abstract

Heparan sulfate proteoglycans (HSPGs) are extracellular macromolecules found on virtually every cell type in eumetazoans. HSPGs are composed of a core protein covalently linked to glycosaminoglycan (GAG) sugar chains that bind and modulate the signaling efficiency of many ligands, including Hedgehog (Hh), Wingless (Wg) and Bone morphogenetic proteins (BMPs). Here, we show that, in Drosophila, loss of HSPGs differentially affects embryonic Hh, Wg and BMP signaling. We find that a stage-specific block to GAG synthesis prevents HSPG expression during establishment of the BMP activity gradient that is crucial for dorsal embryonic patterning. Subsequently, GAG synthesis is initiated coincident with the onset of Hh and Wg signaling which require HSPGs. This temporal regulation is achieved by the translational control of HSPG synthetic enzymes through internal ribosome entry sites (IRESs). IRES-like features are conserved in GAG enzyme transcripts from diverse organisms, suggesting that this represents a novel evolutionarily conserved mechanism for regulating GAG synthesis and modulating growth factor activity.

Author information

Author/s: Bornemann, Douglas J (DJ); Park, Sangbin (S); Phin, Sopheap (S); Warrior, Rahul (R);

Affiliation: Developmental and Cell Biology and Developmental Biology Center, University of California Irvine, Irvine, CA, USA.

Grants: GM067247 (Agency:NIGMS NIH HHS) ; GM5442 (Agency:NIGMS NIH HHS) ; T32 HD-007029 (Agency:NICHD NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Development (Cambridge, England) (Development), published in England. (Language: eng)

Reference: 2008-Mar; vol 135 (issue 6) : pp 1039-47

Dates: Created 2008/02/25; Completed 2008/05/29; Revised 2008/11/21;

PMID: 18256192, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

3' Untranslated Regions 5' Untranslated Regions Animals Animals, Genetically Modified Base Sequence Body Patterning - drug effects Bone Morphogenetic Proteins - metabolism DNA Primers - genetics Drosophila - drug effects; embryology; genetics; metabolism Drosophila Proteins - genetics; metabolism Female

Female Gene Expression Regulation, Developmental Genes, Insect Hedgehog Proteins - genetics; metabolism Heparan Sulfate Proteoglycans - biosynthesis Heparin - pharmacology Membrane Proteins - genetics; metabolism Protein Biosynthesis Proto-Oncogene Proteins - genetics; metabolism Signal Transduction - drug effects Wnt1 Protein

Associated Chemicals: 3' Untranslated Regions (0) ; 5' Untranslated Regions (0) ; Bone Morphogenetic Proteins (0) ; DNA Primers (0) ; Drosophila Proteins (0) ; Hedgehog Proteins (0) ; Heparan Sulfate Proteoglycans (0) ; Membrane Proteins (0) ; Proto-Oncogene Proteins (0) ; Wnt1 Protein (0) ; tout-velu protein, Drosophila (0) ; wg protein, Drosophila (0) ; hedgehog protein, Drosophila (149291-21-4) ; Heparin (9005-49-6)

Related articles

These are the highest related articles currently in the database:

• Planar cell polarity: A bridge too far? 26 Oct 2008
• Drosophila T-box transcription factor Optomotor-blind prevents pathological folding and local overgrowth in wing epithelium through confining Hh signal. 14 May 2007
• Quantitative analysis of Hedgehog gradient formation using an inducible expression system. 5 May 2007
• The endocytic pathway and formation of the Wingless morphogen gradient. 12 Dec 2005
• Distalization of the Drosophila leg by graded EGF-receptor activity. 22 Jul 2002
• Transcription elongation controls cell fate specification in the Drosophila embryo. 29 Apr 2007
• The Snail repressor positions Notch signaling in the Drosophila embryo. 30 Mar 2002
• Wnt signalling: refocusing on Strabismus. 29 Sep 2002
• The glycosyltransferase Fringe promotes Delta-Notch signaling between neurons and glia, and is required for subtype-specific glial gene expression. 30 Jan 2007
• Wingless effects mesoderm patterning and ectoderm segmentation events via induction of its downstream target sloppy paired. 29 Nov 2000

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.