State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.
State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China
Development. 2021 Jan 20;148(2):dev192658. doi: 10.1242/dev.192658.
The paired pharyngeal arch arteries (PAAs) are transient blood vessels connecting the heart with the dorsal aorta during embryogenesis. Although PAA malformations often occur along with pharyngeal pouch defects, the functional interaction between these adjacent tissues remains largely unclear. Here, we report that pharyngeal pouches are essential for PAA progenitor specification in zebrafish embryos. We reveal that the segmentation of pharyngeal pouches coincides spatiotemporally with the emergence of PAA progenitor clusters. These pouches physically associate with pharyngeal mesoderm in discrete regions and provide a niche microenvironment for PAA progenitor commitment by expressing BMP proteins. Specifically, pouch-derived BMP2a and BMP5 are the primary niche cues responsible for activating the BMP/Smad pathway in pharyngeal mesoderm, thereby promoting progenitor specification. In addition, BMP2a and BMP5 play an inductive function in the expression of the gene in PAA progenitors. mutants exhibit a striking failure to specify PAA progenitors and display ectopic expression of head muscle markers in the pharyngeal mesoderm. Therefore, our results support a crucial role for pharyngeal pouches in establishing a progenitor niche for PAA morphogenesis via BMP2a/5 expression.
成对咽弓动脉 (PAAs) 是胚胎发生过程中连接心脏和背主动脉的短暂血管。尽管 PAA 畸形常与咽囊缺陷一起发生，但这些相邻组织之间的功能相互作用在很大程度上仍不清楚。在这里，我们报告咽囊对于斑马鱼胚胎中 PAA 祖细胞的特化是必不可少的。我们揭示了咽囊的分段与 PAA 祖细胞簇的出现时空一致。这些咽囊在离散区域与咽中胚层物理相关，并通过表达 BMP 蛋白为 PAA 祖细胞的定向提供小生境微环境。具体来说，来自咽囊的 BMP2a 和 BMP5 是激活咽中胚层中 BMP/Smad 途径的主要小生境线索，从而促进祖细胞的特化。此外，BMP2a 和 BMP5 在 PAA 祖细胞中 基因的表达中发挥诱导作用。 突变体表现出明显的 PAA 祖细胞特化失败，并在咽中胚层中表现出头肌肉标记物的异位表达。因此，我们的结果支持咽囊通过表达 BMP2a/5 在 PAA 形态发生中建立祖细胞小生境方面的关键作用。
