D'Antonio Maurizio, Michalovich David, Paterson Morris, Droggiti Anna, Woodhoo Ashwin, Mirsky Rhona, Jessen Kristjan R
Department of Anatomy and Developmental Biology, University College London, London, United Kingdom.
Glia. 2006 Apr 1;53(5):501-15. doi: 10.1002/glia.20309.
To elucidate the molecular mechanisms involved in Schwann cell development, we profiled gene expression in the developing and injured rat sciatic nerve. The genes that showed significant changes in expression in developing and dedifferentiated nerve were validated with RT-PCR, in situ hybridisation, Western blot and immunofluorescence. A comprehensive approach to annotating micro-array probes and their associated transcripts was performed using Biopendium, a database of sequence and structural annotation. This approach significantly increased the number of genes for which a functional insight could be found. The analysis implicates agrin and two members of the collapsin response-mediated protein (CRMP) family in the switch from precursors to Schwann cells, and synuclein-1 and alphaB-crystallin in peripheral nerve myelination. We also identified a group of genes typically related to chondrogenesis and cartilage/bone development, including type II collagen, that were expressed in a manner similar to that of myelin-associated genes. The comprehensive function annotation also identified, among the genes regulated during nerve development or after nerve injury, proteins belonging to high-interest families, such as cytokines and kinases, and should therefore provide a uniquely valuable resource for future research.
为阐明雪旺细胞发育过程中涉及的分子机制,我们分析了发育中和损伤的大鼠坐骨神经中的基因表达情况。在发育中和去分化神经中表达有显著变化的基因,通过逆转录聚合酶链反应(RT-PCR)、原位杂交、蛋白质印迹法和免疫荧光法进行了验证。我们使用序列和结构注释数据库Biopendium,对微阵列探针及其相关转录本进行了全面注释。这种方法显著增加了能够找到功能见解的基因数量。分析表明,聚集蛋白和塌陷反应介导蛋白(CRMP)家族的两个成员参与了从雪旺细胞前体向雪旺细胞的转变,而突触核蛋白-1和αB-晶状体蛋白则参与了周围神经髓鞘形成。我们还鉴定出一组通常与软骨形成及软骨/骨发育相关的基因,包括II型胶原蛋白,它们的表达方式与髓鞘相关基因相似。全面的功能注释还在神经发育过程中或神经损伤后受调控的基因中,鉴定出了属于高关注度家族的蛋白质,如细胞因子和激酶,因此应为未来研究提供独特且有价值的资源。