Jul 16, 2005

Cerebral hypoplasia and craniofacial defects in mice lacking heparan sulfate Ndst1 gene function

Development
Kay GrobeJeffrey D Esko

Abstract

Mutant mice bearing a targeted disruption of the heparan sulfate (HS) modifying enzyme GlcNAc N-deacetylase/N-sulfotransferase 1 (Ndst1) exhibit severe developmental defects of the forebrain and forebrain-derived structures, including cerebral hypoplasia, lack of olfactory bulbs, eye defects and axon guidance errors. Neural crest-derived facial structures are also severely affected. We show that properly synthesized heparan sulfate is required for the normal development of the brain and face, and that Ndst1 is a modifier of heparan sulfate-dependent growth factor/morphogen signalling in those tissues. Among the multiple heparan sulfate-binding factors potentially affected in Ndst1 mutant embryos, the facial phenotypes are consistent with impaired sonic hedgehog (Shh) and fibroblast growth factor (Fgf) interaction with mutant heparan sulfate. Most importantly, the data suggest the possibility that defects in heparan sulfate synthesis could give rise to or contribute to a number of developmental brain and facial defects in humans.

  • References
  • Citations101

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations101

Citations

Mentioned in this Paper

Embryo
Hedgehog Proteins
Apoptosis, Intrinsic Pathway
Microphthalmia, Syndromic 6 (Disorder)
Structure of Olfactory Bulb
Pontocerebellar Hypoplasia Type 2A
Hypoplasia
Brain
Shh protein, mouse
Mucopolysaccharidosis III

Related Feeds

Axon Guidance

Axon guidance is a complex neural developmental field that investigates mechanisms through which neurons send out axons to reach its target. Here is the latest research in this domain.