Tschopp Patrick, Tarchini Basile, Spitz François, Zakany Jozsef, Duboule Denis
Department of Zoology and Animal Biology, National Research Centre Frontiers in Genetics, University of Geneva, Sciences III, Geneva, Switzerland.
PLoS Genet. 2009 Mar;5(3):e1000398. doi: 10.1371/journal.pgen.1000398. Epub 2009 Mar 6.
During development of the vertebrate body axis, Hox genes are transcribed sequentially, in both time and space, following their relative positions within their genomic clusters. Analyses of animal genomes support the idea that Hox gene clustering is essential for coordinating the various times of gene activations. However, the eventual collinear ordering of the gene specific transcript domains in space does not always require genomic clustering. We analyzed these complex regulatory relationships by using mutant alleles at the mouse HoxD locus, including one that splits the cluster into two pieces. We show that both positive and negative regulatory influences, located on either side of the cluster, control an early phase of collinear expression in the trunk. Interestingly, this early phase does not systematically impact upon the subsequent expression patterns along the main body axis, indicating that the mechanism underlying temporal collinearity is distinct from those acting during the second phase. We discuss the potential functions and evolutionary origins of these mechanisms, as well as their relationship with similar processes at work during limb development.
在脊椎动物体轴发育过程中，Hox基因按照其在基因组簇中的相对位置，在时间和空间上依次转录。对动物基因组的分析支持了这样一种观点，即Hox基因成簇对于协调基因激活的不同时间至关重要。然而，基因特异性转录结构域在空间上最终的共线性排列并不总是需要基因组成簇。我们通过使用小鼠HoxD基因座的突变等位基因来分析这些复杂的调控关系，其中包括一个将基因簇分成两部分的突变等位基因。我们发现，位于基因簇两侧的正向和负向调控影响，控制着躯干中共线性表达的早期阶段。有趣的是，这个早期阶段并没有系统地影响随后沿主体轴的表达模式，这表明时间共线性的潜在机制与在第二阶段起作用的机制不同。我们讨论了这些机制的潜在功能和进化起源，以及它们与肢体发育过程中类似过程的关系。
