Bates Michael D, Wells James M, Venkatesh Byrappa
Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Gene. 2005 Jun 6;352:45-56. doi: 10.1016/j.gene.2005.03.021.
Hlx is a homeobox transcription factor gene that is expressed in intestinal and hepatic mesenchyme of the developing mouse embryo and is essential for normal intestinal and hepatic development. Because of the morphological and molecular similarities in the development of the digestive system across species, we hypothesized that the Hlx gene and protein sequences and expression patterns would be conserved among vertebrates. Comparison of the Hlx gene orthologues of human, chimpanzee, mouse, rat, pufferfish (Fugu) and zebrafish demonstrates that these six genes share an identical organization with four exons and three introns. Comparison of the inferred Hlx protein sequences from these and three additional species (chick, Spanish ribbed newt and rainbow trout) reveals significant sequence identity, with identical homeodomains. The expression of Hlx in the mesenchyme of developing chick embryos is highly similar to that of mouse. Fugu Hlx is expressed in a tissue-specific manner that is similar though not identical to that of mouse, suggesting a conservation of Hlx function between mammals and birds. The mammalian and fish Hlx genes share a putative 5' upstream enhancer as well as an inverted repeat containing CCAAT boxes on opposite strands that we have previously shown to be important for mouse Hlx gene expression. These results suggest that the function of Hlx and the mechanisms regulating its expression are highly conserved in mammals, birds, amphibians and fish.
Hlx是一种同源框转录因子基因，在发育中的小鼠胚胎的肠道和肝脏间充质中表达，对正常的肠道和肝脏发育至关重要。由于跨物种消化系统发育在形态和分子上具有相似性，我们推测Hlx基因、蛋白质序列及表达模式在脊椎动物中是保守的。对人类、黑猩猩、小鼠、大鼠、河豚（红鳍东方鲀）和斑马鱼的Hlx基因直系同源物进行比较，结果表明这六个基因具有相同的结构，均有四个外显子和三个内含子。对这六个物种以及另外三个物种（鸡、西班牙肋突螈和虹鳟鱼）推导的Hlx蛋白质序列进行比较，发现它们具有显著的序列同一性，且同源结构域相同。Hlx在发育中的鸡胚胎间充质中的表达与小鼠高度相似。河豚Hlx以组织特异性方式表达，虽与小鼠不完全相同，但相似，这表明哺乳动物和鸟类之间Hlx功能具有保守性。哺乳动物和鱼类的Hlx基因共享一个推定的5'上游增强子以及一个包含位于相反链上的CCAAT框的反向重复序列，我们之前已证明该序列对小鼠Hlx基因表达很重要。这些结果表明，Hlx的功能及其表达调控机制在哺乳动物、鸟类、两栖动物和鱼类中高度保守。
