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Glycobiology Advance Access published online on June 8, 2005
Glycobiology, doi:10.1093/glycob/cwi090
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org
Received March 14, 2005
Revised May 24, 2005
Accepted June 5, 2005

Article

Developmental and regional expression of heparan sulfate sulfotransferase genes in the mouse brain

Tomio Yabe 1, Toshihiro Hata 1, Jue He 1, and Nobuaki Maeda 1*

1 Department of Developmental Neuroscience, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan

* To whom correspondence should be addressed.
Nobuaki Maeda, E-mail: maedan{at}tmin.ac.jp


  Abstract

Heparan sulfate (HS) binds with various proteins including growth factors, morphogens and extracellular matrix molecules to regulate their biological functions. These regulatory interactions are considered to be dependent on the structure of HS, which is determined by HS sulfotransferases. To gain insights into the functions of HS sulfotransferases in the development of the nervous system, we examined the expression of these enzymes (3-OST-1,-2, -4; 6-OST-1, -2, -3; NDST-1, -2, -3) by in situ hybridization and real-time RT-PCR. The expression of these genes was spatiotemporally regulated. In the E16 cerebrum, the expression of these genes showed two patterns: (1) selective expression at cortical plate and ventricular zone and (2) wider expression by the cells in the marginal zone, cortical plate, subplate and ventricular zone. At P1, most genes showed similar expression patterns, but after P7, these genes were expressed differentially in a layer-specific manner. On the other hand, in the P1 cerebellum, the external granule cell layer expressed most genes, the expressions of which were downregulated at P7. In contrast, Purkinje cells began to express many of these genes after P7. These complex expression patterns suggest that the structure of HS is altered spatiotemporally for regulating various biological activities in the developing brain including the proliferation of neuronal progenitors, extension of axons and formation of dendrites. We discussed possible functional roles of these sulfotransferases in the signaling of several HS-binding proteins such as fibroblast growth factors, slit, netrin and sonic hedgehog.

Keywords: brain development/heparan sulfate sulfotransferase/in situ hybridization/real-time RT-PCR.
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