Li Feixue, Fu Guoquan, Liu Ying, Miao Xiaoping, Li Yan, Yang Xueqin, Zhang Xiaoyun, Yu Dongliang, Gan Lin, Qiu Mengsheng, Chen Yiping, Zhang Ze, Zhang Zunyi
Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
Department of Molecular Cell Biology, Tulane University, New Orleans, Louisiana, USA.
Mol Cell Biol. 2017 Mar 31;37(8). doi: 10.1128/MCB.00590-16. Print 2017 Apr 15.
Mandibular patterning information initially resides in the epithelium during development. However, how transcriptional regulation of epithelium-derived signaling controls morphogenesis of the mandible remains elusive. Using to target the mandibular epithelium, we ablated transcription factor , resulting in a distally truncated mandible via unbalanced cell apoptosis and decreased cell proliferation in the distal mesenchyme. Loss of caused a lack of cartilage at the distal tip, leading the fusion of two growing mandibular elements surrounding the rostral process of Meckel's cartilage. Loss of results in dysregulation of mesenchymal genes important for morphogenesis of the mandibular arch. We revealed that is required for the activation of epithelial β-catenin signaling via repression of Wnt antagonists. Reactivation of β-catenin in the epithelium of the mutant rescued mandibular morphogenesis through sonic hedgehog (SHH) signaling to the mesenchyme. Furthermore, overexpression of a transgenic hedgehog ligand in the epithelium also partially restored outgrowth of the mandible. These data reveal functional roles for an ISLET1-dependent network integrating β-catenin/SHH signals in mesenchymal cell survival and outgrowth of the mandible during development.
下颌骨模式形成信息在发育过程中最初存在于上皮组织中。然而，上皮来源信号的转录调控如何控制下颌骨的形态发生仍不清楚。利用 靶向下颌上皮组织，我们敲除了转录因子 ，通过远端间充质中不平衡的细胞凋亡和细胞增殖减少导致下颌骨远端截断。 的缺失导致远端尖端缺乏软骨，导致围绕梅克尔软骨喙突的两个生长中的下颌骨元素融合。 的缺失导致对下颌弓形态发生重要的间充质基因失调。我们发现 通过抑制Wnt拮抗剂来激活上皮β-连环蛋白信号是必需的。在 突变体的上皮中β-连环蛋白的重新激活通过向间充质传递音猬因子（SHH）信号挽救了下颌骨形态发生。此外，上皮中转基因刺猬配体的过表达也部分恢复了下颌骨的生长。这些数据揭示了一个依赖ISLET1的网络在发育过程中整合β-连环蛋白/SHH信号在下颌骨间充质细胞存活和生长中的功能作用。
