Mammalian brain morphogenesis and midline axon guidance require heparan sulfate
Mammalian brain morphogenesis and midline axon guidance require heparan sulfate
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DOI：
10.1126/science.1090497
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发表时间：
2003-11-07
期刊：
影响因子：
56.9
通讯作者：
Yamaguchi, Y
中科院分区：
文献类型：
--
作者：
Inatani, M;Irie, F;Yamaguchi, Y
硫酸肝素（HS）是果蝇模式形成过程中形态因子信号传递所必需的，但对其在哺乳动物发育中的生理重要性知之甚少。为了研究HS在哺乳动物中的发育作用，我们在小鼠胚胎脑中有条件地破坏HS聚合酶EXT1。ext1缺失的大脑表现出由多种hs结合形态因子突变引起的模式缺陷。此外，ext1缺失的大脑在主要的联合束中表现出严重的引导错误，揭示了HS在中线轴突引导中的关键作用。这些发现表明，HS对哺乳动物的大脑发育至关重要。
Heparan sulfate (HS) is required for morphogen signaling during Drosophila pattern formation, but little is known about its physiological importance in mammalian development. To de. ne the developmental role of HS in mammalian species, we conditionally disrupted the HS-polymerizing enzyme EXT1 in the embryonic mouse brain. The EXT1-null brain exhibited patterning defects that are composites of those caused by mutations of multiple HS-binding morphogens. Furthermore, the EXT1-null brain displayed severe guidance errors in major commissural tracts, revealing a pivotal role of HS in midline axon guidance. These findings demonstrate that HS is essential for mammalian brain development.