Chou Shen-Ju, Hermesz Edit, Hatta Toshihisa, Feltner Doug, El-Hodiri Heithem M, Jamrich Milan, Mahon Kathleen
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Dev Biol. 2006 Apr 15;292(2):533-45. doi: 10.1016/j.ydbio.2005.12.053. Epub 2006 Mar 9.
TheRpx/Hesx1 homeobox gene is expressed during gastrulation in the anterior visceral and definitive endoderm and the cephalic neural plate. At later stages of development, its expression is restricted to Rathke's pouch, the primordium of the pituitary gland. This expression pattern suggests the presence of at least two distinct regulatory regions that control early and late Rpx transcription. Using transgenic mice, we have demonstrated that regulatory sequences in the 5' upstream region of Rpx are important for early expression in the anterior endoderm and neural plate and regulatory elements in the 3' region are required for late expression in Rathke's pouch. We have found that the genetically required LIM homeodomain-containing proteins Lim1/Lhx1 and Lhx3 are directly involved in the regulation of Rpx transcription. They bind two LIM protein-binding sites in the 5' upstream region of Rpx, which are required for Rpx promoter activity in both mice and Xenopus. Furthermore, we have found that a conserved enhancer in the 3' regulatory sequences of Rpx is not only required, but is also sufficient for the expression of Rpx transgenes in the developing Rathke's pouch.
Rpx/Hesx1 同源框基因在原肠胚形成期在前肠内胚层和确定内胚层以及头侧神经板中表达。在发育后期，其表达局限于垂体原基拉特克囊。这种表达模式表明存在至少两个不同的调控区域，分别控制Rpx的早期和晚期转录。利用转基因小鼠，我们已经证明Rpx 5'上游区域的调控序列对于前肠内胚层和神经板中的早期表达很重要，而3'区域的调控元件是拉特克囊中晚期表达所必需的。我们发现，基因上必需的含LIM同源结构域蛋白Lim1/Lhx1和Lhx3直接参与Rpx转录的调控。它们结合Rpx 5'上游区域的两个LIM蛋白结合位点，这两个位点对于小鼠和非洲爪蟾中的Rpx启动子活性都是必需的。此外，我们发现Rpx 3'调控序列中的一个保守增强子不仅是必需的，而且对于发育中的拉特克囊中Rpx转基因的表达也是足够的。
