Geng Ruishuang, Noda Teppei, Mulvaney Joanna F, Lin Vincent Y W, Edge Albert S B, Dabdoub Alain
Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada.
PLoS One. 2016 Feb 9;11(2):e0148339. doi: 10.1371/journal.pone.0148339. eCollection 2016.
In the inner ear Wnt signaling is necessary for proliferation, cell fate determination, growth of the cochlear duct, polarized orientation of stereociliary bundles, differentiation of the periotic mesenchyme, and homeostasis of the stria vascularis. In neonatal tissue Wnt signaling can drive proliferation of cells in the sensory region, suggesting that Wnt signaling could be used to regenerate the sensory epithelium in the damaged adult inner ear. Manipulation of Wnt signaling for regeneration will require an understanding of the dynamics of Wnt pathway gene expression in the ear. We present a comprehensive screen for 84 Wnt signaling related genes across four developmental and postnatal time points.
We identified 72 Wnt related genes expressed in the inner ear on embryonic day (E) 12.5, postnatal day (P) 0, P6 and P30. These genes included secreted Wnts, Wnt antagonists, intracellular components of canonical signaling and components of non-canonical signaling/planar cell polarity.
A large number of Wnt signaling molecules were dynamically expressed during cochlear development and in the early postnatal period, suggesting complex regulation of Wnt transduction. The data revealed several potential key regulators for further study.
在内耳中，Wnt信号通路对于细胞增殖、细胞命运决定、耳蜗管生长、静纤毛束的极化定向、耳周间充质的分化以及血管纹的稳态是必需的。在新生组织中，Wnt信号通路可驱动感觉区域细胞的增殖，这表明Wnt信号通路可用于再生受损成年内耳的感觉上皮。为实现再生而对Wnt信号通路进行调控，需要了解耳朵中Wnt信号通路基因表达的动态变化。我们针对四个发育阶段和出生后时间点的84个与Wnt信号相关的基因进行了全面筛选。
我们鉴定出72个在胚胎期第12.5天（E12.5）、出生后第0天（P0）、P6和P30在内耳中表达的Wnt相关基因。这些基因包括分泌型Wnts、Wnt拮抗剂、经典信号通路的细胞内成分以及非经典信号通路/平面细胞极性的成分。
在耳蜗发育过程和出生后早期，大量Wnt信号分子动态表达，提示Wnt信号转导存在复杂调控。这些数据揭示了几个有待进一步研究的潜在关键调节因子。
