van den Akker Willem M R, Durston Antony J, Spaink Herman P
Max Planck Institute for Biophysical Chemistry, Department of Molecular Cell Biology, Göttingen, Germany.
Int J Dev Biol. 2010;54(1):55-62. doi: 10.1387/ijdb.082678wv.
Hox proteins are homeobox containing transcription factors that play important roles in patterning the presumptive central nervous system and the axial mesoderm in the early vertebrate embryo. Hox genes are first expressed during gastrula stages and recent studies suggest that their function goes beyond their role as patterning determinants. To improve our understanding of the role of Hox proteins during early vertebrate development, we designed a strategy to identify target genes of the zebrafish hoxb1b using overexpression and whole-genome microarray analysis. We directly compared the hoxb1b microarray data with those resulting from heterologous over-expression of the Xenopus XhoxD1 gene in zebrafish embryos. Both genes are the first expressed hox genes in their respective native embryos and display similar spatial expression patterns. The zebrafish transcriptome was analysed prior to the start of the expression of the endogenous hoxb1b gene and we observed extensive overlap between the hoxb1b and XhoxD1 putative downstream genes suggesting evolutionary functional conservation between these hox genes. Furthermore, genes encoding transcription factors and proteins that are known to be involved in cell adhesion and movement were over-represented among the candidate downstream genes, indicating the involvement of the developmentally earliest expressed hox genes in transcriptional networks and cell movement processes.
Hox蛋白是含有同源框的转录因子,在早期脊椎动物胚胎中对假定的中枢神经系统和轴向中胚层进行模式形成时发挥重要作用。Hox基因在原肠胚阶段首次表达,最近的研究表明它们的功能超出了作为模式决定因素的作用。为了增进我们对Hox蛋白在早期脊椎动物发育过程中作用的理解,我们设计了一种策略,通过过表达和全基因组微阵列分析来鉴定斑马鱼hoxb1b的靶基因。我们将hoxb1b微阵列数据与非洲爪蟾XhoxD1基因在斑马鱼胚胎中的异源过表达所产生的数据进行了直接比较。这两个基因都是各自天然胚胎中最早表达的hox基因,并显示出相似的空间表达模式。在内源性hoxb1b基因开始表达之前,我们对斑马鱼转录组进行了分析,并且我们观察到hoxb1b和XhoxD1假定的下游基因之间存在广泛重叠,这表明这些hox基因之间存在进化上的功能保守性。此外,在候选下游基因中,编码转录因子以及已知参与细胞黏附和运动的蛋白质的基因占比过高,这表明发育上最早表达的hox基因参与了转录网络和细胞运动过程。