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Variant heparan sulfates synthesized in developing mouse brain differentially regulate FGF signaling.
Miriam Ford-Perriss1, Scott E Guimond, Una Greferath
1Department of Anatomy and Cell Biology, University of Melbourne, Victoria, Australia, 3052.
Glycobiology
|December 4, 2002
Summary
Stage-specific heparan sulfate (HS) structures regulate fibroblast growth factor (FGF) signaling during brain development. Differential expression of HS sulfotransferases (HSSTs) generates these distinct HS species, impacting FGF-receptor interactions and neural precursor cell functions.
Area of Science:
- Developmental biology
- Glycobiology
- Neuroscience
Background:
- Heparan sulfates (HSs) are crucial for regulating protein interactions, including growth factors like fibroblast growth factors (FGFs).
- Specific HS sulfation patterns modulate the binding and signaling of FGFs through their tyrosine kinase receptors (FGFRs).
- Previous work identified distinct HS sulfation patterns in embryonic mouse neural precursor cells at embryonic days 10 (E10) and 12 (E12).
Purpose of the Study:
- To investigate how different HS species from E10 and E12 mouse neural precursor cells support signaling of key FGF-FGFR combinations during early brain development.
- To explore the underlying mechanisms, specifically the expression of HS sulfotransferase (HSST) isozymes, responsible for generating stage-specific HS structures.
Main Methods:
- Comparative analysis of HS species from E10 and E12 mouse neural precursor cells.
- Assay of HS species' ability to support FGF8 and FGF2 signaling via specific FGFRs.
- Examination of HSST isozyme expression patterns at E10 and E12.
Main Results:
- E10 HS preferentially activated FGF8 signaling, particularly via FGFR3c, while E12 HS showed no activity for this combination.
- Both E10 and E12 HS supported FGF2 signaling comparably, with a preference for activating FGFR1c.
- Stage-specific combinations of HSST isozymes were identified, correlating with the distinct HS species found at E10 and E12.
Conclusions:
- A stage-specific correlation exists between HS structure and FGF-FGFR mediated signaling in developing brain neural precursor cells.
- Differential expression of HSSTs generates distinct HS species at different developmental stages (E10 vs. E12).
- These variant HS species, through their interactions with FGFs and FGFRs, play a critical role in orchestrating neural proliferation and differentiation.