Developmental shift in expression of netrin receptors in the rat spinal cord: Predominance of UNC-5 homologues in adulthood
Developmental shift in expression of netrin receptors in the rat spinal cord: Predominance of UNC-5 homologues in adulthood
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DOI：
10.1002/jnr.20199
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发表时间：
2004-09-01
影响因子：
4.2
通讯作者：
Kennedy, TE
中科院分区：
文献类型：
--
作者：
Manitt, C;Thompson, KM;Kennedy, TE
Netrin是正常神经发育所需的分泌蛋白质家族。Netrin-1在成年大鼠脊髓和胚胎CNS中以相似的水平表达，表明其有助于成年CNS功能。在这里，我们发现netrin受体dcc，再生蛋白，unc 5 h1，unc 5 h2和unc 5 h3也在成年大鼠脊髓中表达。DCC和再生蛋白的水平较低，检测到在成人相对于胚胎中枢神经系统。相反，与胚胎相比，成人脊髓含有增加水平的α-5同源物。通过北方印迹分析检测到多个mRNA转录本，表明netrin受体可能由选择性剪接的mRNA编码。我们已经确定了一种新的选择性剪接的mRNA编码UNC 5 H1，UNC 5 H1 DeltaTSP 1，它缺乏两个细胞外血小板反应蛋白结构域的第一个。这种新的剪接变体是在早期胚胎CNS中检测到的主要转录物，尽管这两种剪接变体在成人中表达。还检测到先前鉴定的编码DCC和再生蛋白的可变剪接mRNA。Dcc、再生蛋白、unc 5 h1、unc 5 h2和unc 5 h3由神经元亚群表达。unc 5 h2在神经胶质细胞中有强表达。这些发现表明，unc-5同源物构成了netrin-1信号转导在成年脊髓中的主要模式，并可能参与类似轴突排斥的现象，如抑制突起延伸和侧支发芽。(C)2004 Wiley-Liss，Inc.
Netrins are a family of secreted proteins required for normal neural development. Netrin-1 is expressed at similar levels in the adult rat spinal cord and the embryonic CNS, suggesting that it contributes to adult CNS function. Here we show that the netrin receptors dcc, neogenin, unc5h1, unc5h2, and unc5h3 are also expressed in the adult rat spinal cord. Lower levels of DCC and neogenin were detected in the adult relative to the embryonic CNS. Conversely, the adult spinal cord contains increased levels of UNC-5 homologues in comparison with the embryo. Multiple mRNA transcripts detected by Northern blot analysis suggested that netrin receptors might be encoded by alternatively spliced mRNAs. We have identified a novel alternatively spliced mRNA encoding UNC5H1, UNC5H1DeltaTSP1, which lacks the first of the two extracellular thrombospondin domains. This novel splice variant is the major transcript detected in the early embryonic CNS, although both splice variants are expressed in the adult. Previously identified alternatively spliced mRNAs encoding DCC and neogenin were also detected. Dcc, neogenin, unc5h1, unc5h2, and unc5h3 are expressed by subsets of neurons. Robust expression of unc5h2 was found in glia. These findings suggest that unc-5 homologues constitute a major mode of netrin-1 signal transduction in the adult spinal cord and may be involved in phenomena analogous to axon repulsion, such as inhibiting process extension and collateral sprouting. (C) 2004 Wiley-Liss, Inc.