Chung Arthur C-K, Xu Xueping, Niederreither Karen A, Cooney Austin J
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Dev Biol. 2006 May 1;293(1):13-24. doi: 10.1016/j.ydbio.2005.12.017. Epub 2006 Mar 10.
The isthmic organizer, which is located at the midbrain-hindbrain boundary, is important for midbrain development. The mechanism by which the development of the organizer is initiated and maintained is not well understood. Inactivation of the gene encoding the orphan nuclear receptor, GCNF, diminishes the expression of secreted signaling molecules, Fgf8 and Wnt1, the paired box genes Pax2/5, En1/2, and homeodomain transcription factor Gbx2; all of which are essential for isthmic organizer function. In addition, full neuronal differentiation is not observed in the midbrain region of GCNF-/- embryos. Increased cell death may contribute to the loss of midbrain structure in GCNF-/- embryos. These results indicate that GCNF is required for establishment of the isthmic organizer, thereby regulating the midbrain development.
峡部组织者位于中脑-后脑边界，对中脑发育至关重要。组织者发育起始和维持的机制尚不清楚。编码孤儿核受体GCNF的基因失活会减少分泌型信号分子Fgf8和Wnt1、配对盒基因Pax2/5、En1/2以及同源结构域转录因子Gbx2的表达；所有这些对于峡部组织者功能都是必不可少的。此外，在GCNF基因敲除胚胎的中脑区域未观察到完全的神经元分化。细胞死亡增加可能导致GCNF基因敲除胚胎中脑结构的丧失。这些结果表明，GCNF是峡部组织者建立所必需的，从而调节中脑发育。
