Douville Josette M, Wigle Jeffrey T
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB R2H 2A6, Canada.
Can J Physiol Pharmacol. 2007 Jan;85(1):55-65. doi: 10.1139/y06-091.
During embryonic development, the cardiovascular system first forms and then gives rise to the lymphatic vascular system. Homeobox genes are essential for both the development of the blood and lymphatic vascular systems, as well as for their maintenance in the adult. These genes all encode proteins that are transcription factors that contain a well conserved DNA binding motif, the homeodomain. It is through the homeodomain that these transcription factors bind to the promoters of target genes and regulate their expression. Although many homeodomain proteins have been found to be expressed within the vascular systems, little is known about their downstream target genes. This review highlights recent advances made in the identification of novel genes downstream of the homeodomain proteins that are necessary for regulating vascular cellular processes such as proliferation, migration, and endothelial tube formation. Factors known to regulate the functions of vascular cells via modulating the expression of homeobox genes will be discussed. We will also review current methods used to identify and characterize downstream target genes of homeodomain proteins.
在胚胎发育过程中，心血管系统首先形成，然后产生淋巴管系统。同源框基因对于血液和淋巴管系统的发育以及在成体中的维持都至关重要。这些基因都编码作为转录因子的蛋白质，这些转录因子包含一个高度保守的DNA结合基序，即同源结构域。正是通过同源结构域，这些转录因子与靶基因的启动子结合并调节其表达。尽管已发现许多同源结构域蛋白在血管系统中表达，但对其下游靶基因却知之甚少。本综述重点介绍了在鉴定同源结构域蛋白下游新基因方面取得的最新进展，这些新基因对于调节血管细胞过程（如增殖、迁移和内皮管形成）是必需的。还将讨论已知通过调节同源框基因表达来调节血管细胞功能的因子。我们也将综述目前用于鉴定和表征同源结构域蛋白下游靶基因的方法。
