Hooiveld M H, Morgan R, in der Rieden P, Houtzager E, Pannese M, Damen K, Boncinelli E, Durston A J
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
Int J Dev Biol. 1999;43(7):665-74.
Understanding why metazoan Hox/HOM-C genes are expressed in spatiotemporal sequences showing colinearity with their genomic sequence is a central challenge in developmental biology. Here, we studied the consequences of ectopically expressing Hox genes to investigate whether Hox-Hox interactions might help to order gene expression during very early vertebrate embryogenesis. Our study revealed conserved autoregulatory loops for the Hox4 and Hox7 paralogue groups, detected following ectopic expression Hoxb-4 or HOXD4, and Hoxa-7, respectively. We also detected specific induction of 5' posterior Hox genes; Hoxb-5 to Hoxb-9, following ectopic expression of Hoxb-4/HOXD4; Hoxb-8 and Hoxb-9 following ectopic expression of Hoxa-7. Additionally, we observed specific repression of 3' anterior genes, following ectopic expression of Hox4 and Hox7 paralogues. We found that induction of Hoxb-4 and Hoxb-5 by Hoxb-4 can be direct, whereas induction of Hoxb-7 is indirect, suggesting the possibility of an activating cascade. Finally, we found that activation of Hoxb-4 itself and of posterior Hox genes by Hoxb-4 can be both non-cell-autonomous, as well as direct. We believe that our findings could be important for understanding how a highly ordered Hox expression sequence is set up in the early vertebrate embryo.
理解后生动物的Hox/HOM-C基因为何按照与其基因组序列共线性的时空顺序表达，是发育生物学中的一个核心挑战。在此，我们研究了异位表达Hox基因的后果，以探究Hox-Hox相互作用是否有助于在脊椎动物胚胎发育早期对基因表达进行排序。我们的研究揭示了Hox4和Hox7旁系同源基因簇存在保守的自调控环，分别在异位表达Hoxb-4或HOXD4以及Hoxa-7后检测到。我们还检测到5'端后部Hox基因的特异性诱导；在异位表达Hoxb-4/HOXD4后，Hoxb-5至Hoxb-9被诱导；在异位表达Hoxa-7后，Hoxb-8和Hoxb-9被诱导。此外，在异位表达Hox4和Hox7旁系同源基因后，我们观察到3'端前部基因的特异性抑制。我们发现Hoxb-4对Hoxb-4和Hoxb-5的诱导可以是直接的，而对Hoxb-7的诱导是间接的，这表明存在激活级联反应的可能性。最后，我们发现Hoxb-4对其自身以及后部Hox基因的激活既可以是非细胞自主的，也可以是直接的。我们相信我们的发现对于理解早期脊椎动物胚胎中如何建立高度有序的Hox表达序列可能具有重要意义。
