Thomas P, Beddington R
Laboratory of Mammalian Development, National Institute for Medical Research, Mill Hill, London, UK.
Curr Biol. 1996 Nov 1;6(11):1487-96. doi: 10.1016/s0960-9822(96)00753-1.
After implantation, the basic body plan of the mammalian embryo is established during gastrulation when the epithelial founder tissue of the fetus, the epiblast, gives rise to new tissues by ingression through the primitive streak. Formation of the primitive streak defines the caudal aspect of the embryo and thus the anteroposterior axis. Further patterning of this axis has been attributed to signals produced by tissues arising from the primitive streak, and in particular the mesendoderm located along the midline of the embryo is thought to be responsible for the correct anteroposterior subdivision of the neurectoderm as it begins to form the central nervous system (CNS).
In situ hybridization studies show that the onset of expression of the homeobox-containing gene Hesx1 coincides with the formation of the primitive streak, but occurs on the opposite side of the embryo, in a small domain of anterior endoderm. Lineage tracing using a lipophilic fluorescent label shows that the first endoderm cells to express Hesx1 are not destined to contribute to the future embryo, but instead belong to the primitive endoderm lineage and will be displaced by definitive endoderm arising from the primitive streak during gastrulation. Approximately 24 hours after Hesx1 transcripts are first detected in the endoderm, they start to appear in adjacent ectoderm that gives rise to the most anterior component of the developing CNS, the prosencephalon, which continues to express Hesx1. Eventually, Hesx1 transcripts are detectable only in Rathke's pouch as the pituitary starts to develop. Removal of endoderm cells expressing Hesx1 during the earlier stages of gastrulation either prevents or severely curtails the later expression of Hesx1 in ectoderm and neurectoderm, but does not affect gene expression in more caudal regions of the developing CNS.
As overt anterior pattern is present in the visceral embryonic endoderm prior to formation of any axial mesendoderm, a mechanism for bestowing anterior pattern must exist which is independent of primitive streak descendants. Furthermore, correct molecular patterning of the most rostral neurectoderm appears to depend on the presence of this anterior visceral embryonic endoderm during the early stages of gastrulation. We propose that primitive endoderm is responsible for the initial induction of rostral identity in the embryo, and in particular for the correct definition of the future prosencephalic neurectoderm. Subsequently, this identity will be reinforced and maintained by axial mesendoderm when it displaces the visceral embryonic endoderm during the course of gastrulation.
植入后，哺乳动物胚胎的基本身体蓝图在原肠胚形成期间建立，此时胎儿的上皮奠基组织即上胚层通过原始条纹内陷产生新的组织。原始条纹的形成确定了胚胎的尾端，从而确定了前后轴。该轴的进一步模式形成归因于原始条纹产生的组织所产生的信号，特别是位于胚胎中线的中内胚层被认为在神经外胚层开始形成中枢神经系统（CNS）时负责其正确的前后细分。
原位杂交研究表明，含同源框基因Hesx1的表达起始与原始条纹的形成同时发生，但发生在胚胎的另一侧，即前端内胚层的一个小区域。使用亲脂性荧光标记进行的谱系追踪表明，最早表达Hesx1的内胚层细胞并非注定要对未来的胚胎做出贡献，而是属于原始内胚层谱系，并将在原肠胚形成期间被来自原始条纹的确定内胚层所取代。在内胚层首次检测到Hesx1转录本约24小时后，它们开始出现在相邻的外胚层中，该外胚层产生发育中的中枢神经系统最前端的部分即前脑，并持续表达Hesx1。最终，随着垂体开始发育，仅在拉特克囊可检测到Hesx1转录本。在原肠胚形成的早期阶段去除表达Hesx1的内胚层细胞，要么阻止要么严重减少Hesx1在外胚层和神经外胚层中的后期表达，但不影响发育中的中枢神经系统更尾端区域的基因表达。
由于在任何轴向中内胚层形成之前，明显的前部模式就存在于内脏胚胎内胚层中，所以必定存在一种赋予前部模式的机制，该机制独立于原始条纹的后代。此外，最前端神经外胚层的正确分子模式形成似乎取决于原肠胚形成早期这种前部内脏胚胎内胚层的存在。我们提出原始内胚层负责胚胎中头部身份的初始诱导，特别是负责未来前脑神经外胚层的正确定义。随后，当轴向中内胚层在原肠胚形成过程中取代内脏胚胎内胚层时，这种身份将得到加强和维持。
