Ectodermal Wnt controls nasal pit morphogenesis through modulation of the BMP/FGF/JNK signaling axis.
Ectodermal Wnt controls nasal pit morphogenesis through modulation of the BMP/FGF/JNK signaling axis.
复制标题
外胚层 Wnt 通过调节 BMP/FGF/JNK 信号轴来控制鼻凹形态发生。
DOI：
10.1002/dvdy.24376
复制
发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Zhu XJ;Liu Y;Yuan X;Wang M;Zhao W;Yang X;Zhang X;Hsu W;Qiu M;Zhang Z;Zhang Z
WNT3、WNT5A、WNT9B和WNT11基因突变与口腔面部出生缺陷有关，包括人类非综合征性唇裂伴腭裂。然而，Wnt配体的来源及其在口面部形态发生过程中的信号作用仍不清楚。我们利用Foxg1-Cre通过Gpr177/mWls的失活来破坏Wnt的分泌，研究了鼻-面部发育中Wnt产生和信号传导的相关调控。Gpr177的外胚层消融导致严重的面部畸形，这是由于在发育中的面部隆起中WNT、FGF和BMP信号的共同丧失，导致细胞增殖急剧减少和细胞死亡增加。在内陷性鼻坑中，Gpr177的破坏也会对嗅上皮细胞向间充质区迁移产生不利影响。阻断Wnt分泌明显通过调控JNK信号通路损害嗅觉上皮细胞。因此，我们的研究表明，头部外胚层，包括面部外胚层和神经外胚层，是鼻-面部突出发育早期典型和非典型Wnt配体的来源。β-连环蛋白依赖和独立的信号通路对于这些形态发生过程的正常发展都是必需的。
Mutations of WNT3, WNT5A, WNT9B, and WNT11 genes are associated with orofacial birth defects, including non-syndromic cleft lip with cleft palate in humans. However, the source of Wnt ligands and their signaling effects on the orofacial morphogenetic process remain elusive. Using Foxg1-Cre to impair Wnt secretion through the inactivation of Gpr177/mWls, we investigate the relevant regulation of Wnt production and signaling in nasal–facial development. Ectodermal ablation of Gpr177 leads to severe facial deformities resulting from dramatically reduced cell proliferation and increased cell death due to a combined loss of WNT, FGF and BMP signaling in the developing facial prominence. In the invaginating nasal pit, the Gpr177 disruption also causes a detrimental effect on migration of the olfactory epithelial cells into the mesenchymal region. The blockage of Wnt secretion apparently impairs the olfactory epithelial cells through modulation of JNK signaling. Our study thus suggests the head ectoderm, including the facial ectoderm and the neuroectoderm, as the source of canonical as well as noncanonical Wnt ligands during early development of the nasal–facial prominence. Both β-catenin–dependent and –independent signaling pathways are required for proper development of these morphogenetic processes.