The development of the pharyngeal pouches and clefts

咽袋和咽裂的发育

• 批准号: BB/R006199/1
• 负责人: Anthony Graham
• 金额: $ 45.61万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR006199%2F1
• 关键词: development; pharyngeal; pouches; clefts

The aim of this proposal is to investigate key early events in the development of the pharynx. This is an important and intricate region of our bodies but one that is much understudied. During embryogenesis, the pharynx has its origin in a series of bulges found on the surface the head called the pharyngeal arches. Although, the pharyngeal arches are transient structures that only exist during our early development, it is within these structures that the components the adult anatomy of the pharynx are organised; structures that later play roles in feeding, respiration, immune and hormonal activities. Furthermore, defects in the development of the pharyngeal arches lead to numerous birth defects, including branchial arch and cleft anomalies. The first steps in the formation of the pharyngeal arches involves the generation of the pharyngeal pouches which form at specific locations as the inner lining of the pharynx outpockets and contact the overlying tissue resulting in the formation of the pharyngeal clefts. The pouches and clefts are significant structures in organising the development of the pharynx as they act to define the limits of the each of the arches and to direct the development of these structures. The pouches and clefts will also later form important structures in our bodies. The first pharyngeal pouch/cleft contributes to the ear canal and its covering, the tympanic membrane. The second pharyngeal pouch gives rise to the tonsils. The third pouch will develop into the thymus and inferior parathyroid glands, and the fourth pouch gives rise to the superior parathyroid glands and the ultimobranchial bodies which are the source of the C-cells (Calcitonin producing) of the thyroid. The aims of this proposal are to explore key steps in the development of the pharyngeal pouches and clefts. Firstly, we will determine how the pharyngeal pouches are generated and define the cellular mechanisms and signalling pathways that underpin their formation. The next key event that we will scrutinise is the consequence of the contact between the pharyngeal pouches and the overlying ectoderm. Interestingly we have found that this results in a stereotypical series of events that initiates breakdown of the matrix that exists between these two layers and we we want to test the hypothesis that it is the pouches that trigger this process. This could be significant as it may give us insights into other developmental anomalies that occur when endoderm and ectoderm contact each other. The final event that we will analyse is the route through which the pharyngeal pouches and clefts become obscured during development. As mentioned, the pharyngeal arches are only evident for a period during early development and they become obscured as they are enclosed within a cavity, the cervical sinus, which is subsequently eradicated. Thus, our final aim is to identify how this cavity is eradicated and define the cellular and molecular events that underpin this. This is an important step as it is the failure at this paint that results in branchial cleft and sinus anomalies, which are the second most common congenital lesion of the head and neck in children.

本提案的目的是研究咽发育的关键早期事件。这是我们身体的一个重要而复杂的区域，但对它的研究还很不足。在胚胎发育过程中，咽起源于头部表面的一系列凸起，称为咽弓。虽然咽弓是短暂的结构，只存在于我们的早期发育中，但在这些结构中，咽的组成部分被组织起来；这些结构后来在进食、呼吸、免疫和激素活动中起作用。此外，咽弓发育缺陷导致许多出生缺陷，包括鳃裂弓和腭裂异常。咽弓形成的第一步包括咽袋的形成，咽袋在特定的位置形成，作为咽外袋的内衬，并与上面的组织接触，形成咽裂。袋和裂隙是组织咽发育的重要结构，因为它们定义了每个弓的界限并指导这些结构的发育。这些眼袋和裂口后来也会在我们的身体中形成重要的结构。第一个咽袋/咽沟形成耳道及其覆盖层——鼓膜。第二个咽袋产生扁桃体。第三个囊囊会发育为胸腺和下甲状旁腺，第四个囊囊会发育为上甲状旁腺和鳃末体，后者是甲状腺c细胞（产生降钙素）的来源。本提案的目的是探讨咽袋和咽裂发展的关键步骤。首先，我们将确定咽袋是如何产生的，并定义支撑其形成的细胞机制和信号通路。下一个我们要仔细研究的关键事件是咽囊和上覆的外胚层接触的结果。有趣的是，我们发现这导致了一系列刻板的事件，引发了这两层之间的基质的分解，我们想测试这个假设，即是眼袋触发了这个过程。这可能很重要，因为它可以让我们深入了解内胚层和外胚层相互接触时发生的其他发育异常。我们要分析的最后一个事件是咽袋和咽沟在发育过程中变得模糊的路径。如前所述，咽弓只在早期发育的一段时间内是明显的，当它们被封闭在一个腔内，即颈窦内时，它们就变得模糊了，随后就被根除了。因此，我们的最终目标是确定这个空洞是如何被根除的，并定义支撑这一过程的细胞和分子事件。这是很重要的一步，因为这是失败的油漆，导致鳃裂和窦异常，这是第二大最常见的先天性病变的头部和颈部的儿童。

项目成果

A revised terminology for the pharyngeal arches and the arch arteries.

• DOI: 10.1111/joa.13890
• 发表时间: 2023-10
• 期刊: Journal of anatomy
• 影响因子: 2.4

Key separable events in the remodelling of the pharyngeal arches.

• DOI: 10.1111/joa.13850
• 发表时间: 2023-07
• 期刊: Journal of anatomy
• 影响因子: 2.4

Morphogenetic processes in the development and evolution of the arteries of the pharyngeal arches: their relations to congenital cardiovascular malformations.

• DOI: 10.3389/fcell.2023.1259175
• 发表时间: 2023
• 期刊: Frontiers in cell and developmental biology
• 影响因子: 5.5