Mühlfriedel Sven, Kirsch Friederike, Gruss Peter, Stoykova Anastassia, Chowdhury Kamal
Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany.
Dev Biol. 2005 Jul 15;283(2):522-34. doi: 10.1016/j.ydbio.2005.04.033.
The smallest known homeodomain protein, Homeodomain only protein (Hop), was identified and described here as a temporally and spatially restricted gene in the neurogenic regions of the developing murine CNS including the cerebral cortex. Furthermore, an evolutionarily conserved 418 base pair upstream cis-regulatory DNA sequence was found to confine the Hop expression to the CNS of transgenic mice, but not to the heart which is the second major Hop expressing organ Chen, F., Kook, H., Milewski, R., Gitler, A.D., Lu, M.M., Li, J., Nazarian, R., Schnepp, R., Jen, K., Biben, C., Runke, G., Mackay, J.P., Novotny, J., Schwartz, R.J., Harvey, R.P., Mullins, M.C., Epstein, J.A., 2002. Hop is an unusual homeobox gene that modulates cardiac development. Cell 110, 713-723; Shin, C.H., Liu, Z.P., Passier, R., Zhang, C.L., Wang, D.Z., Harris, T.M., Yamagishi, H., Richardson, J.A., Childs, G., Olson, E.N., 2002. Modulation of cardiac growth and development by HOP, an unusual homeodomain protein. Cell 110, 725-735. The forebrain enhancer activity was successfully reproduced in vitro utilizing a combination of the electroporation and the organotypic brain culture method. Using this approach, the minimal requirement for the forebrain-specific enhancer sequence was delineated down to 200 base pairs. We further demonstrate that the Hop enhancer activity is inducible ectopically in a transgenic tissue by wild-type roof plate transplantation in vitro. Thus Hop is regulated in the forebrain by a so far unidentified paracrine signaling factor from the roof plate. Furthermore, the identified enhancer sequence provides an important tool for the targeted expression of transgenes in the medial cortex and the cortical hem.
最小的已知同源域蛋白，即仅含同源域蛋白（Hop），在此被鉴定并描述为发育中的小鼠中枢神经系统（CNS）神经源性区域（包括大脑皮层）中一个在时间和空间上受到限制的基因。此外，还发现一段进化上保守的418碱基对上游顺式调控DNA序列，可将Hop的表达限制在转基因小鼠的中枢神经系统中，但不会限制在心脏中，而心脏是第二个主要表达Hop的器官（Chen, F., Kook, H., Milewski, R., Gitler, A.D., Lu, M.M., Li, J., Nazarian, R., Schnepp, R., Jen, K., Biben, C., Runke, G., Mackay, J.P., Novotny, J., Schwartz, R.J., Harvey, R.P., Mullins, M.C., Epstein, J.A., 2002. Hop是一个调节心脏发育的不寻常同源框基因。《细胞》110, 713 - 723；Shin, C.H., Liu, Z.P., Passier, R., Zhang, C.L., Wang, D.Z., Harris, T.M., Yamagishi, H., Richardson, J.A., Childs, G., Olson, E.N., 2002. 一种不寻常的同源域蛋白HOP对心脏生长和发育的调节。《细胞》110, 725 - 735）。利用电穿孔和器官型脑培养方法相结合，成功地在体外重现了前脑增强子活性。采用这种方法，将前脑特异性增强子序列的最小需求确定为200碱基对。我们进一步证明，通过体外野生型顶板移植，Hop增强子活性可在转基因组织中异位诱导。因此，Hop在前脑中受来自顶板的一种迄今未鉴定的旁分泌信号因子调控。此外，所鉴定的增强子序列为转基因在内侧皮层和皮质下托中的靶向表达提供了一个重要工具。
