Expression of Wnt9b and activation of canonical Wnt signaling during midfacial morphogenesis in mice
Expression of Wnt9b and activation of canonical Wnt signaling during midfacial morphogenesis in mice
复制标题
DOI：
10.1002/dvdy.20723
复制
发表时间：
2006-05-01
影响因子：
2.5
通讯作者：
Jiang, Rulang
中科院分区：
文献类型：
--
作者：
Lan, Yu;Ryan, Rosemary C.;Jiang, Rulang
唇裂伴或不伴腭裂（CLP）是人类最常见的颅面出生缺陷。最近，编码 Wnt 信号分子家族两个成员的 WNT3 和 Wnt9b 基因的突变被发现分别与人类和小鼠的 CLP 相关。为了研究Wnt3和Wnt9b是否直接调节面部发育，我们分析了它们的发育表达模式，发现Wnt3和Wnt9b在小鼠胚胎发生过程中面部形态发生关键阶段的面部外胚层中表达。 Wnt3 mRNA 主要在上颌骨和内侧鼻外胚层中表达，而 Wnt9b mRNA 主要在上颌骨、内侧鼻和外侧鼻外胚层中表达。在唇融合过程中，Wnt9b（而非 Wnt3）在融合内侧鼻突和外侧鼻突之间的上皮缝中表达。此外，我们发现 TOPGAL（经典 Wnt 信号通路激活的转基因报告基因）的表达在唇融合前的内侧鼻、外侧鼻和上颌突的远端区域被特异性激活。在唇融合过程中，内侧和外侧鼻突之间的上皮缝以及融合上皮细胞正下方的面部间质强烈表达 TOPGAL。这些数据与 WNT3(-/-) 人类和 Wnt9b(-/-) 突变小鼠的 CLP 唇表型一起表明 Wnt3 和 Wnt9b 通过经典 Wnt 信号通路发出信号来调节中面部发育和唇融合。发展动力学 235:1448-1454, 2006。(c) 2006 Wiley-Liss, Inc.
Cleft lip with or without cleft palate (CLP) is the most common craniofacial birth defect in humans. Recently, mutations in the WNT3 and Wnt9b genes, encoding two members of the Wnt family of signaling molecules, were found associated with CLP in human and mice, respectively. To investigate whether Wnt3 and Wnt9b directly regulate facial development, we analyzed their developmental expression patterns and found that both Wnt3 and Wnt9b are expressed in the facial ectoderm at critical stages of midfacial morphogenesis during mouse embryogenesis. Whereas Wnt3 mRNA is mainly expressed in the maxillary and medial nasal ectoderm, Wnt9b mRNA is expressed in maxillary, medial nasal, and lateral nasal ectoderm. During lip fusion, Wnt9b, but not Wnt3, is expressed in the epithelial seam between the fusing medial and lateral nasal processes. Furthermore, we found that expression of TOPGAL, a transgenic reporter of activation of canonical Wnt signaling pathway, is specifically activated in the distal regions of the medial nasal, lateral nasal, and maxillary processes prior to lip fusion. During lip fusion, the epithelial seam between the medial and lateral nasal processes as well as the facial mesenchyme directly beneath the fusing epithelia strongly expresses TOPGAL. These data, together with the CLP lip phenotype in WNT3(-/-)humans and Wnt9b(-/-) mutant mice, indicate that Wnt3 and Wnt9b signal through the canonical Wnt signaling pathway to regulate midfacial development and lip fusion. Developmental Dynamics 235:1448-1454, 2006. (c) 2006 Wiley-Liss, Inc.