Yabe Tomio, Hata Toshihiro, He Jue, Maeda Nobuaki
Department of Developmental Neuroscience, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan.
Glycobiology. 2005 Oct;15(10):982-93. doi: 10.1093/glycob/cwi090. Epub 2005 Jun 8.
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-O-sulfotransferase-1 [3-OST-1], -2, -4; 6-OST-1, -2, -3; and N-deacetylase /N-sulfotransferase-1 [NDST-1], -2, -3) by in situ hybridization and real-time reverse transcription-polymerase chain reaction (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 (CP) and ventricular zone (VZ) and (2) wider expression by the cells in the marginal zone (MZ), CP, subplate (SP), and VZ. At P1, most genes showed similar expression patterns, but after P7, these genes were expressed differentially in a layer-specific manner. In the P1 cerebellum, the external granule cell layer (EGL) expressed most genes, the expressions of which were down-regulated 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 discuss possible functional roles of these sulfotransferases in the signaling of several HS-binding proteins such as fibroblast growth factors, slit, netrin, and sonic hedgehog.
硫酸乙酰肝素（HS）与多种蛋白质结合，包括生长因子、形态发生素和细胞外基质分子，以调节它们的生物学功能。这些调节性相互作用被认为依赖于HS的结构，而HS的结构由HS硫酸转移酶决定。为了深入了解HS硫酸转移酶在神经系统发育中的功能，我们通过原位杂交和实时逆转录-聚合酶链反应（RT-PCR）检测了这些酶（3-O-硫酸转移酶-1 [3-OST-1]、-2、-4；6-OST-1、-2、-3；以及N-脱乙酰酶/N-硫酸转移酶-1 [NDST-1]、-2、-3）的表达。这些基因的表达在时空上受到调控。在胚胎第16天的大脑中，这些基因的表达呈现两种模式：（1）在皮质板（CP）和脑室区（VZ）选择性表达；（2）在边缘区（MZ）、CP、亚板（SP）和VZ的细胞中广泛表达。在出生后第1天（P1），大多数基因表现出相似的表达模式，但在P7之后，这些基因以层特异性方式差异表达。在P1的小脑中，外颗粒细胞层（EGL）表达大多数基因，这些基因的表达在P7时下调。相反，浦肯野细胞在P7之后开始表达许多这些基因。这些复杂多样的表达模式表明，HS的结构在时空上发生改变，以调节发育中大脑的各种生物学活动，包括神经元祖细胞的增殖、轴突的延伸和树突的形成。我们讨论了这些硫酸转移酶在几种与HS结合的蛋白质（如成纤维细胞生长因子、Slit、Netrin和音猬因子）信号传导中的可能功能作用。
