BMP4 signaling is involved in the generation of inner ear sensory epithelia.
BMP4 signaling is involved in the generation of inner ear sensory epithelia.
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DOI：
10.1186/1471-213x-5-16
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发表时间：
2005-08-17
影响因子：
--
通讯作者：
Heller, S
中科院分区：
文献类型：
--
作者：
Li, HW;Corrales, CE;Wang, ZM;Zhao, YL;Wang, YC;Liu, H;Heller, S
BMP 4在内耳早期感觉器官中的稳健表达表明这种信号蛋白在听觉和前庭感觉上皮的诱导和发育过程中可能起作用。纯合子BMP 4-/-动物在内耳感觉器官发育之前死亡，这排除了通过简单的基因敲除实验确定BMP 4在这些器官中的作用。在这里，我们使用鸡耳囊培养系统进行定量研究内耳细胞类型的发展，并表明，毛细胞和支持细胞的生成显着减少时，BMP信号被阻断，无论是与其拮抗剂头蛋白或通过使用可溶性BMP受体。相反，我们观察到的毛细胞的数量增加时，培养的耳囊与外源性BMP 4处理。BMP 4处理另外促使Pax-2蛋白在增殖的感觉上皮祖细胞中下调，导致祖细胞增殖减少。我们的研究结果表明，BMP 4在鸡内耳感觉上皮形成过程中参与了两个事件：第一，诱导从增殖感觉上皮祖细胞向分化上皮细胞的转变，第二，促进发育中的感觉上皮中毛细胞的分化。
The robust expression of BMP4 in the incipient sensory organs of the inner ear suggests possible roles for this signaling protein during induction and development of auditory and vestibular sensory epithelia. Homozygous BMP4-/- animals die before the inner ear's sensory organs develop, which precludes determining the role of BMP4 in these organs with simple gene knockout experiments. Here we use a chicken otocyst culture system to perform quantitative studies on the development of inner ear cell types and show that hair cell and supporting cell generation is remarkably reduced when BMP signaling is blocked, either with its antagonist noggin or by using soluble BMP receptors. Conversely, we observed an increase in the number of hair cells when cultured otocysts were treated with exogenous BMP4. BMP4 treatment additionally prompted down-regulation of Pax-2 protein in proliferating sensory epithelial progenitors, leading to reduced progenitor cell proliferation. Our results implicate BMP4 in two events during chicken inner ear sensory epithelium formation: first, in inducing the switch from proliferative sensory epithelium progenitors to differentiating epithelial cells and secondly, in promoting the differentiation of hair cells within the developing sensory epithelia.