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Specific heparan sulfate structures involved in retinal axon targeting
Atsushi Irie1, Edwin A Yates, Jeremy E Turnbull
1Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Development (Cambridge, England)
|January 10, 2002
Summary
Specific heparan sulfate (HS) sequences, particularly those with 2-O- and 6-O-sulfate groups, are crucial for guiding axons in the developing brain. These distinct HS structures regulate retinotectal axon targeting.
Area of Science:
- Neuroscience
- Developmental Biology
- Glycobiology
Background:
- Heparan sulfate (HS) is a structurally diverse molecule abundant in the developing brain.
- HS binds to axon guidance molecules and plays a role in neural development.
- The precise structural requirements of HS for axon guidance are not well understood.
Purpose of the Study:
- To identify the specific structural characteristics of HS that influence axon targeting in the developing brain.
- To elucidate the role of HS structural diversity in retinotectal axon guidance.
Main Methods:
- Utilized an in vivo brain assay in Xenopus.
- Inhibited endogenous HS sulfation using chlorate.
- Examined the effects of chemically modified heparins and purified heparin saccharides.
- Performed in situ hybridization to determine the expression patterns of HS sulfotransferases.
Main Results:
- Inhibiting HS sulfation caused axons to bypass their target (tectum).
- Specific sulfate groups (2-O- and 6-O-) were identified as critical for inducing aberrant axon targeting.
- Bypass-inducing activity correlated with distinct HS structures, especially combinations of 2-O- and 6-O-sulfate groups.
- HS 6-O-sulfotransferase showed regional expression, while 2-O-sulfotransferase was broadly expressed.
Conclusions:
- Specific HS sequences, not just overall composition, are essential for regulating retinotectal axon targeting.
- Regionalized biosynthesis of particular HS structures is important for guiding axons to the tectum.