Investigating the mechanisms that restrict the extra-embryonic Yolk Syncytial Layer

研究限制胚胎外卵黄合胞层的机制

• 批准号: BB/X001539/1
• 负责人: Karuna Sampath
• 金额: $ 53.03万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX001539%2F1
• 关键词: Investigating; mechanisms; restrict; extra; embryonic

The normal development of many animals depends on cells that make the animal ("embryonic cells") as well as supporting cells that do not form a part of the final animal form per se ("extra-embryonic" cells). For instance, the human placenta is a supporting "extra-embryonic" tissue which is essential for normal human embryo development. In many fish species, an extra-embryonic tissue called the yolk syncytial layer (YSL) develops within a shared yolk cytoplasm. The YSL does not become a part of the fully-formed animal, but is a crucial source of nutrition and signals for the developing fish. If the developing fish embryo is separated from the yolk and YSL at very early stages, the embryo develops abnormally. Although the YSL is crucial for normal development, how it forms and how the YSL is controlled is not well understood. Protein factors deposited by the mother into the egg are thought to control YSL formation, but to date, only a few molecules have been found and how they act in YSL development is not well understood. We found that Zebrafish embryos lacking the proteins Igf2bp3 and Ybx1 have an abnormally expanded YSL at the expense of the embryo proper, leading to disastrous consequences for the embryo. How Igf2bp3 and Ybx1 control YSL formation is not known. Zebrafish embryos are transparent at early stages, making it possible to see the YSL as it forms. We will film the YSL as it forms in normal zebrafish embryos and compare to embryos lacking these proteins. We will investigate how some key cell communication pathways are controlled by these proteins during YSL formation. We will identify the key molecules through which Igf2bp3 and Ybx1 control development of the YSL. Through these strategies, we will find out how Igf2bp3 and Ybx1 function in YSL formation in zebrafish. Both the proteins are present in many animals. The mechanisms that we identify might be involved in extra-embryonic tissue formation in other fish. Therefore, the work is likely to be of broad relevance to extra-embryonic development across animal species.

许多动物的正常发育取决于构成动物的细胞（“胚胎细胞”）以及不构成最终动物形态本身的一部分的支持细胞（“胚胎外”细胞）。例如，人类胎盘是一种支持性“胚胎外”组织，对于人类胚胎的正常发育至关重要。在许多鱼类中，称为卵黄合胞体层 (YSL) 的胚胎外组织在共享的卵黄细胞质内发育。 YSL 不会成为完全形成的动物的一部分，但它是发育中的鱼类的重要营养和信号来源。如果正在发育的鱼胚胎在很早的阶段就与卵黄和 YSL 分离，则胚胎发育异常。尽管 YSL 对于正常发育至关重要，但它如何形成以及如何控制 YSL 尚不清楚。人们认为，母亲沉积到卵子中的蛋白质因子可以控制 YSL 的形成，但迄今为止，只发现了少数分子，而且它们在 YSL 发育中的作用尚不清楚。我们发现，缺乏 Igf2bp3 和 Ybx1 蛋白的斑马鱼胚胎会出现 YSL 异常扩张，但会损害胚胎本身，从而给胚胎带来灾难性的后果。 Igf2bp3 和 Ybx1 如何控制 YSL 形成尚不清楚。斑马鱼胚胎在早期阶段是透明的，因此可以看到 YSL 的形成。我们将拍摄正常斑马鱼胚胎中形成的 YSL，并与缺乏这些蛋白质的胚胎进行比较。我们将研究 YSL 形成过程中这些蛋白质如何控制一些关键的细胞通讯途径。我们将确定 Igf2bp3 和 Ybx1 控制 YSL 发育的关键分子。通过这些策略，我们将了解 Igf2bp3 和 Ybx1 在斑马鱼 YSL 形成中如何发挥作用。这两种蛋白质都存在于许多动物体内。我们发现的机制可能与其他鱼类的胚胎外组织形成有关。因此，这项工作可能与动物物种的胚胎外发育具有广泛的相关性。