Temporal and spatial regulation of α6 integrin expression during the development of the cochlear-vestibular ganglion
Temporal and spatial regulation of α6 integrin expression during the development of the cochlear-vestibular ganglion
复制标题
DOI：
10.1002/cne.21302
复制
发表时间：
2007-06-10
影响因子：
2.5
通讯作者：
Davies, Dawn
中科院分区：
文献类型：
--
作者：
Davies, Dawn
耳蜗-前庭神经节（CVG）神经元支配内耳的感觉毛细胞，其来源于发育早期的耳上皮。成神经细胞从邻近的细胞分离，迁移到间充质中，在那里它们合并形成神经节复合体，然后将突起送回上皮。细胞迁移和神经元突起形成涉及细胞与细胞外基质中的其他细胞和蛋白质的相互作用的变化，这些变化由细胞表面表达的粘附分子（包括整合素）协调。我研究了表达模式的α 6整合素亚基在早期发展的CVG使用免疫组织化学和逆转录聚合酶链反应（RT-PCR）在小鼠组织切片，耳囊肿，神经节外植体。在胚胎第10.5天（E），α 6整合素在耳上皮中表达，但在迁移的成神经细胞中不表达。重要的是，α 6的丢失与上皮细胞的退出有关，而不是神经元的决定，揭示了与细胞环境密切相关的分化线索。神经胶质和神经元表型的标记物显示，在此阶段CVG中存在的α 6表达细胞是神经嵴起源的神经胶质。通过E12.5，神经节中的α 6表达随着神经元突起的加工而增加。应用于耳囊培养的神经胶质细胞的情况下，免疫组化显示，神经元的过程仍然是α 6-阴性在这个发展阶段，并证实，α 6表达密切并列的神经胶质细胞。α 6表达的时空调制表明，在内耳神经支配的早期发展过程中，这种整合素的作用发生了变化。
The neurons of the cochlear-vestibular ganglion (CVG) that innervate the sensory hair cells of the inner ear are derived from the otic epithelium early in development. Neuroblasts detach from neighboring cells, migrate into the mesenchyme where they coalesce to form the ganglion complex, then send processes back into the epithelium. Cell migration and neuronal process formation involve changes in cellular interactions with other cells and proteins in the extracellular matrix that are orchestrated by cell surface-expressed adhesion molecules, including the integrins. I studied the expression pattern of the alpha 6 integrin subunit during the early development of the CVG using immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR) in murine tissue sections, otocyst, and ganglion explants. At embryonic day (E)10.5 alpha 6 integrin was expressed in the otic epithelium but not in migrating neuroblasts. Importantly, the loss of alpha 6 was associated with exit from the epithelium, not neuronal determination, revealing differentiation cues acutely associated with the cellular environment. Markers of glial and neuronal phenotype showed that alpha 6-expressing cells present in the CVG at this stage were glia of neural crest origin. By E12.5 alpha 6 expression in the ganglion increased alongside the elaboration of neuronal processes. Immunohistochemistry applied to otocyst cultures in the absence of glia revealed that neuronal processes remained alpha 6-negative at this developmental stage and confirmed that alpha 6 was expressed by closely apposed glia. The spatiotemporal modulation of alpha 6 expression suggests changing roles for this integrin during the early development of inner ear innervation.