Kolle Gabriel, Jansen Annemieke, Yamada Toshiya, Little Melissa
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Dev Dyn. 2003 Jan;226(1):107-11. doi: 10.1002/dvdy.10204.
The novel mammalian gene Crim1 encodes a transmembrane bound protein with similarity to the secreted bone morphogenetic protein (BMP) antagonists, vertebrate Chordin, and its Drosophila homologue short gastrulation. Crim1 is expressed in the neural tube in mouse in a restricted pattern, but its function in central nervous system development is largely unknown. We isolated the chicken Crim1 orthologue and analyzed its expression in the developing neural tube. Chicken CRIM1 shares strong homology to human/mouse CRIM1 and C. elegans CRIM1-like proteins. Crim1 is expressed in a similar but not identical pattern to that in the developing spinal cord of mouse, including the notochord, floor plate, motor neurons, and the roof plate. Unlike follistatin, a secreted inhibitor of BMPs, in ovo electroporation of CRIM1, as a full-length transmembrane bound or secreted ectodomain was not sufficient to disrupt early patterning of the neural tube. However, ectodomain CRIM1 overexpression leads to an approximate 50% decrease in populations of specific ventral neuronal populations, including ISL-1(+) motor neurons, CHX-10(+) V1, and EN-1(+) V2 interneurons.
新发现的哺乳动物基因Crim1编码一种跨膜结合蛋白，该蛋白与分泌型骨形态发生蛋白（BMP）拮抗剂、脊椎动物脊索蛋白及其果蝇同源物短原肠胚形成蛋白相似。Crim1在小鼠神经管中以一种受限模式表达，但其在中枢神经系统发育中的功能很大程度上未知。我们分离出鸡的Crim1直系同源物，并分析了其在发育中的神经管中的表达。鸡的CRIM1与人/小鼠CRIM1以及秀丽隐杆线虫CRIM1样蛋白具有很强的同源性。Crim1在发育中的小鼠脊髓中的表达模式相似但不完全相同，包括脊索、底板、运动神经元和顶板。与BMP的分泌型抑制剂卵泡抑素不同，在鸡胚中电穿孔导入全长跨膜结合形式或分泌型胞外结构域形式的CRIM1，不足以破坏神经管的早期模式形成。然而，胞外结构域CRIM1的过表达导致特定腹侧神经元群体数量减少约50%，包括ISL-1(+)运动神经元、CHX-10(+) V1和EN-1(+) V2中间神经元。
