A mutation in zebrafish affecting a localized cellular function required for normal ear development.
A mutation in zebrafish affecting a localized cellular function required for normal ear development.
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斑马鱼的突变影响正常耳朵发育所需的局部细胞功能。
DOI：
10.1006/dbio.1996.0272
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Grunwald,DJ
中科院分区：
文献类型：
--
作者：
Riley,BB;Grunwald,DJ
斑马鱼作为研究内耳发育的模型系统具有很大的潜力，因为遗传技术是高效的，并且内耳发育是斑马鱼胚胎发生的显著和可操作的特征。在这里，我们描述了一个半致死性显性突变，termedmonolith（mnl），专门扰乱前（椭圆囊）耳石在发展中的耳朵的形成分析。除了椭圆囊耳石缺陷外，在突变胚胎中耳的所有结构在形态上都是正常的，包括后耳石和所有感觉上皮。几个穗标记基因（msxC、msxD和dlx 3）的表达模式在突变体中也表现正常。为了鉴定受mnl突变影响的细胞类型，通过将染料标记的+/+细胞移植到未标记的mnl/mnl宿主胚胎中来产生嵌合体。大约一半的嵌合体正常形成椭圆囊耳石，表明移植的野生型细胞拯救了它们的突变宿主。+/+细胞命运的详细分析显示，几乎所有的嵌合体，其中+/+细胞形成支持细胞的椭圆囊感觉上皮被救出。相比之下，形成其他细胞类型（如毛细胞）或定殖宿主其他区域的野生型细胞不足以促进救援。这些数据表明，支持细胞所需的正常耳石形成，提供了第一个实验建立的脊椎动物感觉上皮细胞的支持细胞的作用。这些数据还首次明确表明耳石的形成在耳的不同区域是由局部细胞功能独立控制的。
Zebrafish holds great potential as a model system for studying inner ear development because genetic techniques are highly efficient and inner ear development is a conspicuous and manipulable feature of zebrafish embryogenesis. Here we describe analysis of a semilethal dominant mutation, termedmonolith(mnl), that specifically perturbs formation of the anterior (utricular) otolith in the developing ear. Other than the utricular otolith deficiency, all structures in the ear appear morphologically normal in mutant embryos, including posterior otoliths and all sensory epithelia. Expression patterns of several ear marker genes (msxC, msxD,anddlx3) also appear normal in the mutant. To identify the cell type(s) affected by themnlmutation, chimeras were generated by transplanting dye-labeled +/+ cells into unlabeledmnl/mnlhost embryos. Roughly half of such chimeras formed utricular otoliths normally, indicating that the transplanted wild-type cells rescued their mutant hosts. Detailed analysis of +/+ cell fates revealed that virtually all chimeras in which +/+ cells formed support cells in the utricular sensory epithelium were rescued. In contrast, wild-type cells forming other cell types (such as hair cells) or colonizing other regions of the host were not sufficient to facilitate rescue. These data indicate that support cells are required for normal otolith formation, providing the first experimentally established role for support cells in vertebrate sensory epithelia. The data also provide the first clear indication that otolith formation is controlled independently in different regions of the ear by localized cellular functions.