BMP signaling is required for nkx2.3-positive pharyngeal pouch progenitor specification in zebrafish
BMP signaling is required for nkx2.3-positive pharyngeal pouch progenitor specification in zebrafish
复制标题
斑马鱼 nkx2.3 阳性咽袋祖细胞规范需要 BMP 信号传导。
DOI：
10.1371/journal.pgen.1007996
复制
发表时间：
2019-02-01
期刊：
影响因子：
4.5
通讯作者：
Wang, Qiang
中科院分区：
文献类型：
--
作者：
Li, Linwei;Ning, Guozhu;Wang, Qiang
咽囊是由前肠内胚层发育而成的一系列外囊，对颅面骨骼以及甲状旁腺和胸腺等重要结构的形成至关重要。然而，咽囊祖细胞是否存在于发育中的肠管中仍然未知。在这里，利用细胞谱系追踪和转基因消融技术，我们在斑马鱼胚胎中鉴定了一群nkx2.3（+）囊祖细胞，并证明了外胚层BMP 2b对其特化的基本要求。在体节早期，nkx2.3（+）细胞位于咽内胚层的外侧区域，除了一个表达pdgfa而不是nkx2.3的亚群外，其他细胞都形成了囊上皮。一个小规模的化学抑制剂的屏幕显示，BMP信号是必要的，以指定这些祖细胞。功能丧失分析显示，在咽外胚层中表达的BMP 2b激活内胚层细胞中的Smad效应子以诱导nkx2.3（+）祖细胞。总的来说，我们的研究提供了在体内的证据袋祖细胞的存在和突出的重要性，BMP 2b信号在祖specification.Author摘要咽袋是必不可少的颅面骨骼的形成，以及几个重要的结构，如甲状旁腺和胸腺，但其祖细胞是否存在于发展中的肠管仍然未知。我们的研究提供了体内证据，在体节早期，nkx2.3（+）细胞存在于侧咽内胚层，并产生囊上皮。我们进一步揭示，外胚层BMP2b是必不可少的激活内胚层细胞中的Smad效应，从而促进袋祖规范。总的来说，我们的发现揭示了咽袋发育的细胞和分子机制。
Pharyngeal pouches, a series of outpocketings that bud from the foregut endoderm, are essential to the formation of craniofacial skeleton as well as several important structures like parathyroid and thymus. However, whether pharyngeal pouch progenitors exist in the developing gut tube remains unknown. Here, taking advantage of cell lineage tracing and transgenic ablation technologies, we identified a population of nkx2.3(+) pouch progenitors in zebrafish embryos and demonstrated an essential requirement of ectodermal BMP2b for their specification. At early somite stages, nkx2.3(+) cells located at lateral region of pharyngeal endoderm give rise to the pouch epithelium except a subpopulation expressing pdgfa rather than nkx2.3. A small-scale screen of chemical inhibitors reveals that BMP signaling is necessary to specify these progenitors. Loss-of-function analyses show that BMP2b, expressed in the pharyngeal ectoderm, actives Smad effectors in endodermal cells to induce nkx2.3(+) progenitors. Collectively, our study provides in vivo evidence for the existence of pouch progenitors and highlights the importance of BMP2b signaling in progenitor specification.Author summary Pharyngeal pouches are essential to the formation of craniofacial skeleton as well as several important structures like parathyroid and thymus, but whether their progenitors exist in the developing gut tube remains unknown. Our study provide in vivo evidence that, in the early somite stages, nkx2.3(+) cells are present in the lateral pharyngeal endoderm and give rise to the pouch epithelium. We further reveal that ectodermal BMP2b is essential for the activation of Smad effectors in endodermal cells, thereby facilitating pouch progenitor specification. Collectively, our discoveries shed new light on the cellular and molecular mechanisms of pharyngeal pouch development.