Forlani Sylvie, Lawson Kirstie A, Deschamps Jacqueline
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
Development. 2003 Aug;130(16):3807-19. doi: 10.1242/dev.00573.
Early sequential expression of mouse Hox genes is essential for their later function. Analysis of the relationship between early Hox gene expression and the laying down of anterior to posterior structures during and after gastrulation is therefore crucial for understanding the ontogenesis of Hox-mediated axial patterning. Using explants from gastrulation stage embryos, we show that the ability to express 3' and 5' Hox genes develops sequentially in the primitive streak region, from posterior to anterior as the streak extends, about 12 hours earlier than overt Hox expression. The ability to express autonomously the earliest Hox gene, Hoxb1, is present in the posterior streak region at the onset of gastrulation, but not in the anterior region at this stage. However, the posterior region can induce Hoxb1 expression in these anterior region cells. We conclude that tissues are primed to express Hox genes early in gastrulation, concomitant with primitive streak formation and extension, and that Hox gene inducibility is transferred by cell to cell signalling. Axial structures that will later express Hox genes are generated in the node region in the period that Hox expression domains arrive there and continue to spread rostrally. However, lineage analysis showed that definitive Hox codes are not fixed at the node, but must be acquired later and anterior to the node in the neurectoderm, and independently in the mesoderm. We conclude that the rostral progression of Hox gene expression must be modulated by gene regulatory influences from early on in the posterior streak, until the time cells have acquired their stable positions along the axis well anterior to the node.
小鼠Hox基因的早期顺序表达对其后期功能至关重要。因此，分析原肠胚形成期间及之后早期Hox基因表达与前后结构形成之间的关系，对于理解Hox介导的轴向模式形成的个体发生至关重要。利用原肠胚形成阶段胚胎的外植体，我们发现3'和5'Hox基因的表达能力在原条区域依次发展，随着原条从后向前延伸，比明显的Hox表达早约12小时。最早的Hox基因Hoxb1自主表达的能力在原肠胚形成开始时存在于原条后部区域，但此时在前部区域不存在。然而，后部区域可以诱导这些前部区域细胞中Hoxb1的表达。我们得出结论，组织在原肠胚形成早期就准备好表达Hox基因，这与原条的形成和延伸同时发生，并且Hox基因的诱导能力通过细胞间信号传递。在Hox表达域到达并继续向头端扩散的时期，将在节点区域产生后来表达Hox基因的轴向结构。然而，谱系分析表明，确定的Hox编码在节点处并不固定，而是必须在神经外胚层中节点后方稍后获得，并且在中胚层中独立获得。我们得出结论，Hox基因表达的头端进展必须从原条后部早期就受到基因调控影响的调节，直到细胞沿着轴在节点前方很远的位置获得其稳定位置时为止。
