Requirements for FGF3 and FGF10 during inner ear formation
Requirements for FGF3 and FGF10 during inner ear formation
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DOI：
10.1242/dev.00881
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发表时间：
2003-12-01
期刊：
影响因子：
4.6
通讯作者：
Schimmang, T
中科院分区：
文献类型：
--
作者：
Alvarez, Y;Alonso, MT;Schimmang, T
成纤维细胞生长因子（FGF）基因家族的成员控制脊椎动物的身体计划和器官发生的形成。FGF 3在发育中的后脑中表达，并且已经显示参与不同脊椎动物物种（包括斑马鱼、非洲爪蟾、鸡和小鼠）的内耳发育。在小鼠中，通过同源重组将新霉素抗性基因插入Fgf3基因导致耳泡分化期间的严重发育缺陷。我们已经解决了确切的作用，FGF3和其他FGF家族成员在形成过程中的小鼠内耳使用的损失和增益的功能实验。我们产生了一个新的突变等位基因缺乏整个FGF 3编码区，但令人惊讶地发现，没有证据表明严重缺陷，无论是在内耳发育或成熟的感觉器官，这表明在其形成过程中的其他FGF家族成员的功能参与。FGF10在转基因小鼠发育中的后脑中的异位表达导致异位囊泡的形成，表达一些耳标记基因，从而表明FGF10在耳囊泡形成期间的作用。在小鼠胚胎发生过程中FGF10的表达分析揭示了在发育中的后脑中表达的高度动态模式，与FGF3表达部分重叠，并且与内耳的形成一致。然而，已报道FGF10突变小鼠在内耳分化期间仅显示轻度缺陷。因此，我们创建了FGF 3和FGF 10的双突变小鼠，其形成严重减少的耳囊，表明这些FGF的冗余作用，作为耳囊形成的神经信号组合起作用。
Members of the fibroblast growth factor (FGF) gene family control formation of the body plan and organogenesis in vertebrates. FGF3 is expressed in the developing hindbrain and has been shown to be involved in inner ear development of different vertebrate species, including zebrafish, Xenopus, chick and mouse. In the mouse, insertion of a neomycin resistance gene into the Fgf3 gene via homologous recombination results in severe developmental defects during differentiation of the otic vesicle. We have addressed the precise roles of FGF3 and other FGF family members during formation of the murine inner ear using both loss- and gain-of-function experiments. We generated a new mutant allele lacking the entire FGF3-coding region but surprisingly found no evidence for severe defects either during inner ear development or in the mature sensory organ, suggesting the functional involvement of other FGF family members during its formation. Ectopic expression of FGF10 in the developing hindbrain of transgenic mice leads to the formation of ectopic vesicles, expressing some otic marker genes and thus indicating a role for FGF10 during otic vesicle formation. Expression analysis of FGF10 during mouse embryogenesis reveals a highly dynamic pattern of expression in the developing hindbrain, partially overlapping with FGF3 expression and coinciding with formation of the inner ear. However, FGF10 mutant mice have been reported to display only mild defects during inner ear differentiation. We thus created double mutant mice for FGF3 and FGF10, which form severely reduced otic vesicles, suggesting redundant roles of these FGFs, acting in combination as neural signals for otic vesicle formation.