Pharyngeal pouches provide a niche microenvironment for arch artery progenitor specification.
Pharyngeal pouches provide a niche microenvironment for arch artery progenitor specification.
复制标题
咽袋为弓动脉祖细胞的规范提供了一个利基微环境。
DOI：
10.1242/dev.192658
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发表时间：
2021-01-20
期刊：
影响因子：
--
通讯作者：
Wang Q
中科院分区：
文献类型：
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作者：
Mao A;Zhang M;Li L;Liu J;Ning G;Cao Y;Wang Q
成对的咽弓动脉（PAAs）是胚胎发育过程中连接心脏和背主动脉的短暂血管。虽然PAA畸形经常沿着咽囊缺损，但这些相邻组织之间的功能相互作用仍不清楚。在这里，我们报告，咽囊是必不可少的PAA祖规格在斑马鱼胚胎。我们发现，分割的咽袋在时空上与PAA祖集群的出现相吻合。这些囊在物理上与咽部中胚层的离散区域相关联，并通过表达BMP蛋白为PAA祖细胞定型提供微环境。具体而言，囊衍生的BMP 2a和BMP 5是负责激活咽中胚层中的BMP/Smad通路的主要生态位线索，从而促进祖细胞特化。此外，BMP 2a和BMP 5在PAA祖细胞中对cloche基因npas 4l的表达起诱导作用。cloche突变体表现出明显的失败，指定PAA祖细胞和显示头肌标记物在咽中胚层异位表达。因此，我们的研究结果支持咽囊在通过BMP 2a/5表达建立PAA形态发生的祖生态位中的关键作用。总结：咽囊来源的BMP 2a和BMP 5是斑马鱼胚胎发育过程中诱导弓状动脉祖细胞特化的关键生态位线索。
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 cloche gene npas4l in PAA progenitors. cloche 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. Summary: Pharyngeal pouch-derived BMP2a and BMP5 are the key niche cues that induce arch artery progenitor specification during zebrafish embryonic development.