The development of semicircular canals in the inner ear: role of FGFs in sensory cristae
The development of semicircular canals in the inner ear: role of FGFs in sensory cristae
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DOI：
10.1242/dev.01292
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发表时间：
2004-09-01
期刊：
影响因子：
4.6
通讯作者：
Wu, DK
中科院分区：
文献类型：
--
作者：
Chang, W;Brigande, JV;Wu, DK
在脊椎动物内耳中，检测头部角度运动的能力在于三个半规管及其感觉组织，嵴。这三个运河形成的分子机制在很大程度上是未知的。在斑马鱼和小鼠中发现的这种前庭器官的畸形通常涉及运河和嵴。虽然有例子的突变体只有缺陷的运河，很少有突变体有正常的运河没有一些以前的感觉组织规范，这表明感觉组织，嵴，可能会诱导其非感觉成分，半规管的形成。我们使用荧光亲脂性染料（DiI）对鸡的垂直管袋进行了命运映射，该垂直管袋产生了前后管，并确定了与每个预期嵴相邻的管发生区，该区域对应于管袋中的骨形态发生蛋白2（Bmp 2）阳性结构域。使用逆转录病毒或珠子增加成纤维细胞生长因子（FGF）的功能获得和珠浸泡成纤维细胞生长因子抑制剂SU 5402的功能丧失的实验，我们表明，在嵴FGF促进运河的发展，通过上调Bmp 2。我们推测，在嵴FGF诱导/上调Bmp 2表达的运河生成区。异位FGF治疗可将管袋中的一些细胞从预期的共同囊袋转化为管样命运。因此，我们提供了第一个分子证据，即感觉器官指导相关的非感觉组件，半规管，在脊椎动物内耳的发展。
In the vertebrate inner ear, the ability to detect angular head movements lies in the three semicircular canals and their sensory tissues, the cristae. The molecular mechanisms underlying the formation of the three canals are largely unknown. Malformations of this vestibular apparatus found in zebrafish and mice usually involve both canals and cristae. Although there are examples of mutants with only defective canals, few mutants have normal canals without some prior sensory tissue specification, suggesting that the sensory tissues, cristae, might induce the formation of their non-sensory components, the semicircular canals. We fate-mapped the vertical canal pouch in chicken that gives rise to the anterior and posterior canals, using a fluorescent, lipophilic dye (DiI), and identified a canal genesis zone adjacent to each prospective crista that corresponds to the Bone morphogenetic protein 2 (Bmp2)-positive domain in the canal pouch. Using retroviruses or beads to increase Fibroblast Growth Factors (FGFs) for gain-of-function and beads soaked with the FGF inhibitor SU5402 for loss-of-function experiments, we show that FGFs in the crista promote canal development by upregulating Bmp2. We postulate that FGFs in the cristae induce a canal genesis zone by inducing/upregulating Bmp2 expression. Ectopic FGF treatments convert some of the cells in the canal pouch from the prospective common crus to a canal-like fate. Thus, we provide the first molecular evidence whereby sensory organs direct the development of the associated non-sensory components, the semicircular canals, in vertebrate inner ears.