Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Mech Dev. 2011 Jan-Feb;128(1-2):104-15. doi: 10.1016/j.mod.2010.11.003. Epub 2010 Nov 18.
Wnt activity is critical in craniofacial morphogenesis. Dysregulation of Wnt/β-catenin signaling results in significant alterations in the facial form, and has been implicated in cleft palate phenotypes in mouse and man. In zebrafish, we show that wnt9a is expressed in the pharyngeal arch, oropharyngeal epithelium that circumscribes the ethmoid plate, and ectodermal cells superficial to the lower jaw structures. Alcian blue staining of morpholino-mediated knockdown of wnt9a results in loss of the ethmoid plate, absence of lateral and posterior parachordals, and significant abrogation of the lower jaw structures. Analysis of cranial neural crest cells in the sox10:eGFP transgenic demonstrates that the wnt9a is required early during pharyngeal development, and confirms that the absence of Alcian blue staining is due to absence of neural crest derived chondrocytes. Molecular analysis of genes regulating cranial neural crest migration and chondrogenic differentiation suggest that wnt9a is dispensable for early cranial neural crest migration, but is required for chondrogenic development of major craniofacial structures. Taken together, these data corroborate the central role for Wnt signaling in vertebrate craniofacial development, and reveal that wnt9a provides the signal from the pharyngeal epithelium to support craniofacial chondrogenic morphogenesis in zebrafish.
Wnt 活性在颅面形态发生中至关重要。Wnt/β-连环蛋白信号的失调导致面部形态的显著改变，并与小鼠和人类的腭裂表型有关。在斑马鱼中，我们表明 wnt9a 在咽弓、环绕筛板的口咽上皮以及下颌结构下方的外胚层细胞中表达。wnt9a 的 morpholino 介导敲低导致筛板缺失、侧后副脊索缺失以及下颌结构显著破坏。在 sox10:eGFP 转基因的颅神经嵴细胞分析中，wnt9a 在咽发育早期是必需的，并证实 Alcian 蓝染色的缺失是由于缺少神经嵴来源的软骨细胞。对调节颅神经嵴迁移和软骨分化的基因的分子分析表明，wnt9a 对于早期颅神经嵴迁移不是必需的，但对于主要颅面结构的软骨发生发育是必需的。总之，这些数据证实了 Wnt 信号在脊椎动物颅面发育中的核心作用，并表明 wnt9a 从咽上皮提供信号，以支持斑马鱼颅面软骨发生形态发生。
