PLC-IP3信号促进斑马鱼神经丘感觉毛细胞形成
PLC-IP3 signaling promotes sensory hair cell formation in zebrafish neuromast.
文献信息
| PMID | 42714214 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Chao Yang |
| 作者单位 | Co-innovation Center of Neuroregeneration, Nantong Laboratory of Development and Diseases, School of Life Sciences, Institute of Special Environmental Medicine, Nantong University, Nantong 226001, China. |
| 期刊 | Development (Cambridge, England) |
| SCI 分区 | Q1 |
| IF | 4.6 |
| 研究类型 | 基础研究 · 基础／转化 |
| 所属专科 | 耳科 |
中文摘要
感音神经性听力损失主要由感觉毛细胞（HCs）不可逆损伤引起，而再生策略仍受限于HC形成效率低下以及新生成细胞功能成熟不完全。在此，我们利用药物扰动、单细胞转录组测序和斑马鱼神经丘的遗传分析，鉴定出磷酸肌醇特异性磷脂酶C（PLC）信号是HC发育和成熟的细胞内调节因子。激活PLC信号增加HC数量和FM4-64标记，而抑制则减少HC数量并损害感觉驱动行为。单细胞轨迹和RNA速率分析显示，PLC信号不改变谱系拓扑结构，但促进沿HC分化轨迹的进展。在PLC亚型中，plcd4a在HCs中选择性富集，并且是促进HC形成和成熟所必需的。机制上，通路扰动实验表明PLC-IP3信号在HC分化过程中与Notch和Wnt通路功能性相互作用。总之，这些发现支持一个模型，即PLC信号促进HC分化和成熟相关进展，为可能促进HC再生的机制提供了见解。
英文摘要
Sensorineural hearing loss primarily results from irreversible damage to sensory hair cells (HCs), and regenerative strategies remain limited by inefficient HC formation and incomplete functional maturation of newly generated cells. Here, using pharmacological perturbation, single-cell transcriptomics sequencing, and genetic analysis in zebrafish neuromasts, we identify phosphoinositide-specific phospholipase C (PLC) signaling as an intracellular regulator of HC development and maturation. Activation of PLC signaling increases the number of HCs and FM4-64 labeling, whereas inhibition reduces HC number and impairs sensory-driven behavior. Single-cell trajectory and RNA velocity analyses reveal that PLC signaling does not alter lineage topology, but promotes progression along the HC differentiation trajectory. Among PLC isoforms, plcd4a is selectively enriched in HCs and is necessary to promote HC formation and maturation. Mechanistically, pathway perturbation experiments suggest that PLC-IP3 signaling functionally interacts with Notch and Wnt pathways during HC differentiation. Together, these findings support a model in which PLC signaling promotes HC differentiation and maturation-associated progression, providing insight into mechanisms that may promote HC regeneration.