Rojas Diego A, Perez-Munizaga Daniela A, Centanin Lazaro, Antonelli Marcelo, Wappner Pablo, Allende Miguel L, Reyes Ariel E
Facultad de Ciencias de la Salud, Universidad Diego Portales, Av. Ejército Libertador 141, Santiago, Chile.
Gene Expr Patterns. 2007 Jan;7(3):339-45. doi: 10.1016/j.modgep.2006.08.002. Epub 2006 Aug 15.
Hypoxia-inducible factors (HIFs) regulate gene expression in response to hypoxia and in vertebrates they are known to participate in several developmental processes, including angiogenesis, vasculogenesis, heart and central nervous system development. Over the last decade, major progress in unraveling the molecular mechanisms that mediate regulation of HIF proteins by oxygen tension has been reported, but our knowledge on their developmental regulation during embryogenesis in model organisms is limited. Expression of hif-1alpha and hif-2alpha genes has been characterized during normal mouse development and they were found to be expressed from stages E7.5, later in E9.5 and E15.5 in several different tissues such as the brain, heart and blood vessels. However, there is no detailed temporal information on their expression at other embryonic stages, even though orthologous genes have been described in several different vertebrate species. In this study, we describe the cloning and detailed expression pattern of zebrafish hif-1alpha and hif-2alpha genes. Sequence analysis revealed that zebrafish Hif proteins are highly homologous to other vertebrate orthologues. Zebrafish hif-1alpha and hif-2alpha are both expressed throughout development in discrete territories in a dynamic pattern. Interestingly, in the notochord the expression of hif-1alpha is switched off, while hif-2alpha transcription is turned on, signifying that the two genes might have partially overlapping, although non-redundant functions in development. This is the first time that a detailed comparison of the expression of hif-1alpha and hif-2alpha is directly assessed in a vertebrate model system throughout development.
缺氧诱导因子（HIFs）可响应缺氧情况调节基因表达，在脊椎动物中，已知它们参与多种发育过程，包括血管生成、血管发生、心脏和中枢神经系统发育。在过去十年中，已有报道在揭示氧张力介导HIF蛋白调节的分子机制方面取得了重大进展，但我们对其在模式生物胚胎发育过程中的发育调控的了解仍然有限。hif-1α和hif-2α基因在正常小鼠发育过程中的表达已得到表征，发现它们从E7.5阶段开始表达，随后在E9.5和E15.5阶段在几种不同组织（如脑、心脏和血管）中表达。然而，即使在几种不同的脊椎动物物种中已经描述了直系同源基因，关于它们在其他胚胎阶段表达的详细时间信息仍然缺乏。在本研究中，我们描述了斑马鱼hif-1α和hif-2α基因的克隆及详细表达模式。序列分析表明，斑马鱼Hif蛋白与其他脊椎动物的直系同源物高度同源。斑马鱼hif-1α和hif-2α在整个发育过程中均在离散区域以动态模式表达。有趣的是，在脊索中，hif-1α的表达关闭，而hif-2α的转录开启，这表明这两个基因在发育过程中可能具有部分重叠但并非冗余的功能。这是首次在脊椎动物模型系统中直接评估hif-1α和hif-2α在整个发育过程中的表达详细比较。
