Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA, 52242, USA.
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA, 52242, USA.
Dev Biol. 2022 Sep;489:122-133. doi: 10.1016/j.ydbio.2022.06.010. Epub 2022 Jun 19.
Craniofacial skeletal elements are derived from cranial neural crest cells (CNCCs), which migrate along discrete paths and populate distinct pharyngeal arches, structures that are separated by the neighboring endodermal pouches (EPs). Interactions between the CNCCs and the endoderm are critical for proper craniofacial development. In zebrafish, integrin α5 (Itga5) functions in the endoderm to regulate formation of specifically the first EP (EP1) and the development of the hyoid cartilage. Here we show that fibronectin (Fn), a major component of the extracellular matrix (ECM), is also required for these developmental processes, and that the penetrance of defects in mutants is temperature-dependent. fn1a embryos exhibited defects that are similar to, but much more severe than, those of itga5 embryos, and a loss of integrin av (itgav) function enhanced both endoderm and cartilage defects in itga5 embryos, suggesting that Itga5 and Itgav cooperate to transmit signals from Fn to regulate the development of endoderm and cartilage. Whereas the endodermal defects in itga5; itga5v double mutant embryos were comparable to those of fn1a mutants, the cartilage defects were much milder. Furthermore, Fn assembly was detected in migrating CNCCs, and the epithelial organization and differentiation of CNCC-derived arches were impaired in fn1a embryos, indicating that Fn1 exerts functions in arch development that are independent of Itga5 and Itgav. Additionally, reduction of itga5 function in fn1a embryos led to profound defects in body axis elongation, as well as in endoderm and cartilage formation, suggesting that other ECM proteins signal through Itga5 to regulate development of the endoderm and cartilage. Thus, our studies reveal that Fn1a and Itga5 have both overlapping and independent functions in regulating development of the pharyngeal endoderm and cartilage.
颅面骨骼元素来源于颅神经嵴细胞（CNCCs），这些细胞沿着离散的路径迁移，并填充到不同的咽弓中，这些结构由相邻的内胚层囊（EPs）隔开。CNCCs 和内胚层之间的相互作用对于正常的颅面发育至关重要。在斑马鱼中，整合素α5（Itga5）在内胚层中发挥作用，调节第一个内胚层囊（EP1）和舌骨软骨的形成。在这里，我们表明，纤连蛋白（Fn）是细胞外基质（ECM）的主要成分之一，对于这些发育过程也是必需的，并且突变体缺陷的穿透率是温度依赖性的。fn1a 胚胎表现出的缺陷与 itga5 胚胎相似，但更为严重，并且整合素 av（itgav）功能的丧失增强了 itga5 胚胎中外胚层和软骨缺陷，表明 Itga5 和 Itgav 合作从 Fn 传递信号，以调节外胚层和软骨的发育。尽管 itga5; itga5v 双突变体胚胎的内胚层缺陷与 fn1a 突变体相当，但软骨缺陷要轻得多。此外，在迁移的 CNCCs 中检测到 Fn 组装，并且 fn1a 胚胎中 CNCC 衍生的弓的上皮组织和分化受到损害，表明 Fn1 在弓发育中发挥了独立于 Itga5 和 Itgav 的功能。此外，在 fn1a 胚胎中降低 itga5 功能导致身体轴伸长以及内胚层和软骨形成的严重缺陷，表明其他 ECM 蛋白通过 Itga5 信号调节内胚层和软骨的发育。因此，我们的研究表明，Fn1a 和 Itga5 在调节咽内胚层和软骨的发育中具有重叠和独立的功能。
