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Heparan sulfate Ndst1 gene function variably regulates multiple signaling pathways during mouse development.
- Source :
-
Developmental dynamics : an official publication of the American Association of Anatomists [Dev Dyn] 2007 Feb; Vol. 236 (2), pp. 556-63. - Publication Year :
- 2007
-
Abstract
- Disruption of heparan sulfate (HS) synthesis in vertebrate development causes malformations that are composites of those caused by mutations of multiple HS binding growth factors and morphogens. We previously reported severe developmental defects of the forebrain and the skull in mutant mice bearing a targeted disruption of the heparan sulfate-generating enzyme GlcNAc N-deacetylase/GlcN N-sulfotransferase 1 (Ndst1). Here, we further characterize the molecular mechanisms leading to frontonasal dysplasia in Ndst1 mutant embryos and describe additional malformations, including impaired spinal and cranial neural tube fusion and skeletal abnormalities. Of the numerous proteins that bind HS, we show that impaired fibroblast growth factor, Hedgehog, and Wnt function may contribute to some of these phenotypes. Our findings, therefore, suggest that defects in HS synthesis may contribute to multifactor types of congenital developmental defects in humans, including neural tube defects.
- Subjects :
- Alkaline Phosphatase metabolism
Animals
Apoptosis genetics
Cell Proliferation
DNA Primers
Embryonic Development genetics
Fibroblast Growth Factors metabolism
Mice
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction genetics
Bone Diseases, Developmental genetics
Embryonic Development physiology
Nervous System Malformations genetics
Signal Transduction physiology
Sulfotransferases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1058-8388
- Volume :
- 236
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Developmental dynamics : an official publication of the American Association of Anatomists
- Publication Type :
- Academic Journal
- Accession number :
- 17183530
- Full Text :
- https://doi.org/10.1002/dvdy.21038