Frohman M A, Boyle M, Martin G R
Department of Anatomy, School of Medicine, University of California, San Francisco 94143.
Development. 1990 Oct;110(2):589-607. doi: 10.1242/dev.110.2.589.
It is rapidly becoming accepted that the vertebrate neural tube, in particular the hindbrain, develops into a segmented structure. After segment formation, cells in the neural tube do not cross segmental boundaries, and segment-specific gene expression is observed. However, it is not known what positional cues instruct the neural tube to express genes in this restricted manner. We have cloned a murine homeobox-containing gene, Hox-2.9, whose expression in the neural tube at E9.5 is restricted to a segment of the hindbrain known as rhombomere 4. A study of its expression pattern earlier in development revealed that prior to the start of neurulation (E7.5) Hox-2.9 is expressed within a posterior to the embryonic mesoderm that will participate in hindbrain formation. With the onset of neurulation, expression then becomes detectable in the neural plate as well, but only in the part that overlies the Hox-2.9-expressing mesoderm; it is not detected in the more anterior neuroectoderm that will form the future midbrain and forebrain. On the basis of these findings, we propose that the mesoderm is providing cues that serve to instruct the overlying neuroectoderm with respect to its position along the anteroposterior axis and that Hox-2.9 participates in or reflects this process. As neurulation continues and individual segments form, a second phase of expression is detected in the neural tube in which high levels of Hox-2.9 transcripts become restricted to rhombomere 4. Hox-2.9 expression is also detected in the developing branchial arch units of the hindbrain region, in a pattern that suggests to us that here, too, mesoderm is providing a localized signal that induces Hox-2.9 expression, in this case in endoderm of the pharynx and in superficial ectoderm. In general, we interpret the expression patterns of Hox-2.9 in the hindbrain region as suggesting that the specific mechanisms of pattern formation in mammals are fundamentally similar to those of amphibians and avians - i.e. anteroposterior positional information is acquired by mesoderm, mesoderm induces positional values within (neuro-) ectoderm and endoderm, and both events occur within a restricted window of time.
脊椎动物的神经管，尤其是后脑，逐渐发育成节段性结构，这一观点正迅速被人们接受。节段形成后，神经管中的细胞不会跨越节段边界，并且会观察到节段特异性基因表达。然而，尚不清楚是什么位置线索指导神经管以这种受限的方式表达基因。我们克隆了一个含有小鼠同源异型框的基因Hox - 2.9，其在E9.5时在神经管中的表达局限于后脑的一个节段，即菱脑节4。对其在发育早期表达模式的研究表明，在神经胚形成开始之前（E7.5），Hox - 2.9在将参与后脑形成的胚胎中胚层后部表达。随着神经胚形成的开始，在神经板中也能检测到表达，但仅在覆盖表达Hox - 2.9的中胚层的部分；在将形成未来中脑和前脑的更前端神经外胚层中未检测到。基于这些发现，我们提出中胚层正在提供线索，用于指导覆盖其上的神经外胚层沿前后轴的位置，并且Hox - 2.9参与或反映了这一过程。随着神经胚形成的继续和各个节段的形成，在神经管中检测到表达的第二阶段，其中高水平的Hox - 2.9转录本局限于菱脑节4。在后脑区域发育中的鳃弓单位中也检测到Hox - 2.9的表达，其模式向我们表明，在这里中胚层同样提供了一个局部信号，诱导Hox - 2.9的表达，在这种情况下是在咽部内胚层和表面外胚层中。总体而言，我们将Hox - 2.9在后脑区域的表达模式解释为表明哺乳动物中模式形成的特定机制与两栖动物和鸟类的基本相似——即前后位置信息由中胚层获得，中胚层在（神经）外胚层和内胚层中诱导位置值，并且这两个事件都发生在有限的时间窗口内。
