Developmental and regional expression of heparan sulfate sulfotransferase genes in the mouse brain.
Developmental and regional expression of heparan sulfate sulfotransferase genes in the mouse brain.
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DOI：
10.1093/glycob/cwi090
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发表时间：
2005-10
期刊：
影响因子：
4.3
通讯作者：
T. Yabe;T. Hata;Jue He;N. Maeda
中科院分区：
文献类型：
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作者：
T. Yabe;T. Hata;Jue He;N. Maeda
硫酸乙酰肝素（HS）与多种蛋白质结合，包括生长因子、形态因子和细胞外基质分子，以调节其生物学功能。这些调控相互作用被认为依赖于HS的结构，这是由HS硫转移酶决定的。为了深入了解HS硫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 -硫转移酶-1 [3-OST-1]， -2, -4; 6-OST-1, -2, -3； n-去乙酰化酶/ n-硫转移酶-1 [NDST-1]， -2, -3）的表达。这些基因的表达受时空调控。在E16脑组织中，这些基因的表达呈现两种模式：(1)皮质板（CP）和心室区（VZ）的选择性表达；(2)边缘区（MZ）、CP、亚板（SP）和VZ的细胞广泛表达。在P1时，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的方式表达差异。在P1小脑中，外颗粒细胞层（EGL）表达了大部分基因，这些基因在P7表达下调。相反，浦肯野细胞在P7后开始表达这些基因中的许多。这些复杂的表达模式表明，HS的结构在时空上发生改变，以调节大脑发育中的各种生物活动，包括神经元祖细胞的增殖、轴突的延伸和树突的形成。我们讨论了这些硫转移酶在几种hs结合蛋白（如成纤维细胞生长因子、狭缝、网蛋白和超音hedgehog）的信号传导中的可能功能作用。
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.