Centre for Developmental Neurobiology, King's College London, London, UK.
School of Life Sciences, University of Sussex, Brighton, UK.
J Anat. 2023 Jul;243(1):100-109. doi: 10.1111/joa.13850. Epub 2023 Feb 23.
The pharyngeal arches are a series of bulges on the lateral surface of the embryonic head. They are a defining feature of the most conserved, the phylotypic, stage of vertebrate development. In many vertebrate clades, the segmental arrangement of the pharyngeal arches is translated into the iterative anatomy of the gill arches. However, in amniotes the pharyngeal arches undergo a rearrangement during development and the segmental organisation of the pharynx is lost. This remodelling involves the expansion of the second arch which comes to overlie the more posterior arches. A transient sinus forms between the expanded second arch and the posterior arches, that is then lost, and the posterior arches are internalised. The morphogenesis of the second arch has been viewed as being central to this remodelling. Yet little is known about this process. Therefore, in this study, we have characterised the development of the second arch. We show that as the second arch expands, its posterior margin forms a leading edge and that the mesenchymal cells subjacent to this are in an elevated proliferative state. We further show that the posterior marginal epithelium is the site of expression of three key developmental signalling molecules: BMP7, FGF8 and SHH, and that their expression continues throughout the period of expansion. Using a novel approach, we have been able to simultaneously inhibit these three pathways, and we find that when this is done the second arch fails to establish its caudal projection and that there is a loss of proliferation in the posterior mesenchymal cells of the second arch. We have further used this manipulation to ask if the internalisation of the posterior arches is dependent upon the expansion of the second arch. We find that it is not-the posterior arches are still internalised when the expansion of the second arch is curtailed. We further show that while the collapse of the sinus is dependent upon thyroid hormone signalling, that this is not the case for the internalisation of the posterior pouches. Thus, the internalisation of the posterior arches is not dependent on the expansion of the second arch or on the collapse of the sinus. Finally, we show that the termination of expansion of the second arch correlates with a burst of morphogenetic cell death suggesting a mechanism for ending this. Thus, while it has long been thought that it is the morphogenesis of the second arch that drives the remodelling of the pharyngeal arches, we show that this is not the case. Rather the remodelling of the pharyngeal arches is a composite process that can split into contemporaneous but separate events: the expansion of the second arch, the internalisation of the posterior arches and the collapse of the sinus.
咽弓是胚胎头部侧面的一系列隆起。它们是脊椎动物发育中最保守的、典型阶段的特征。在许多脊椎动物类群中，咽弓的节段排列被转化为鳃弓的迭代解剖结构。然而，在羊膜动物中，咽弓在发育过程中会重新排列，咽的节段组织丢失。这种重塑涉及到第二弓的扩张，第二弓覆盖在更后的弓上。在扩张的第二弓和后弓之间形成一个短暂的窦，然后消失，后弓被内化。第二弓的形态发生被认为是这种重塑的核心。然而，人们对这个过程知之甚少。因此，在这项研究中，我们对第二弓的发育进行了描述。我们表明，随着第二弓的扩张，其后缘形成一个前缘，而位于其后缘下方的间充质细胞处于升高的增殖状态。我们进一步表明，后缘上皮是三个关键发育信号分子：BMP7、FGF8 和 SHH 的表达部位，并且它们的表达贯穿于扩张期。通过一种新的方法，我们能够同时抑制这三个途径，我们发现当这样做时，第二弓不能建立其尾部投影，并且第二弓的后间充质细胞的增殖减少。我们进一步利用这种操作来询问后弓的内化是否依赖于第二弓的扩张。我们发现并非如此——当第二弓的扩张受到限制时，后弓仍然被内化。我们进一步表明，虽然窦的塌陷依赖于甲状腺激素信号，但后囊的内化并非如此。因此，后弓的内化不依赖于第二弓的扩张或窦的塌陷。最后，我们表明第二弓扩张的终止与形态发生性细胞死亡的爆发相关，这表明了一种结束扩张的机制。因此，虽然长期以来人们一直认为是第二弓的形态发生推动了咽弓的重塑，但我们表明事实并非如此。相反，咽弓的重塑是一个复合过程，可以分为同时但独立的事件：第二弓的扩张、后弓的内化和窦的塌陷。
