Zhang Haoran, Xie Junjie, So Karl Kam Hei, Tong Ka Kui, Sae-Pang Jearn Jang, Wang Li, Tsang Sze Lan, Chan Wood Yee, Wong Elaine Yee Man, Sham Mai Har
School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.
Front Physiol. 2021 Jan 11;11:612230. doi: 10.3389/fphys.2020.612230. eCollection 2020.
Craniofacial morphogenesis depends on proper migration of neural crest cells and their interactions with placodes and other cell types. genes provide positional information and are important in patterning the neural crest and pharyngeal arches (PAs) for coordinated formation of craniofacial structures. genes are expressed in the surface ectoderm and epibranchial placodes, their roles in the pharyngeal epithelium and their downstream targets in regulating PA morphogenesis have not been established. We altered the code in the pharyngeal region of the mutant, in which is driven to ectopically expressed in domain in the second pharyngeal arch (PA2). In the transgenic mutant, ectopic expression was restricted to the surface ectoderm, including the proximal epibranchial placodal region and the distal pharyngeal epithelium. The mutants displayed hypoplasia of PA2, multiple neural crest-derived facial skeletal and nerve defects. Interestingly, we found that in the mutant, expression of the Notch ligand was specifically up-regulated in the ectodermal pharyngeal epithelial cells of PA2. By molecular experiments, we demonstrated that Hoxb3 could bind to an upstream genomic site S2 and directly regulate expression. In the mutant, elevated expression of in the pharyngeal epithelium led to abnormal cellular interaction and deficiency of neural crest cells migrating into PA2. In summary, we showed that regulates Jag1 expression and proposed a model of pharyngeal epithelium and neural crest interaction during pharyngeal arch development.
颅面形态发生依赖于神经嵴细胞的正常迁移及其与基板和其他细胞类型的相互作用。基因提供位置信息,在为颅面结构的协调形成对神经嵴和咽弓(PAs)进行模式化方面很重要。基因在表面外胚层和鳃上基板中表达,它们在咽上皮中的作用及其在调节咽弓形态发生中的下游靶点尚未确定。我们改变了突变体咽区域的编码,其中在第二咽弓(PA2)的区域中被驱动异位表达。在转基因突变体中,异位表达仅限于表面外胚层,包括近端鳃上基板区域和远端咽上皮。突变体显示PA2发育不全,多个神经嵴衍生的面部骨骼和神经缺陷。有趣的是,我们发现在突变体中,Notch配体的表达在PA2的外胚层咽上皮细胞中特异性上调。通过分子实验,我们证明Hoxb3可以结合上游基因组位点S2并直接调节表达。在突变体中,咽上皮中表达的升高导致异常的细胞相互作用和迁移到PA2中的神经嵴细胞缺乏。总之,我们表明调节Jag1表达,并提出了咽弓发育过程中咽上皮与神经嵴相互作用的模型。