BMP-signaling regulates the generation of hair-cells
BMP-signaling regulates the generation of hair-cells
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DOI：
10.1016/j.ydbio.2006.01.001
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发表时间：
2006-04-01
影响因子：
2.7
通讯作者：
Giraldez, F
中科院分区：
文献类型：
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作者：
Pujades, C;Kamaid, A;Giraldez, F
骨形态发生蛋白（BMP）是一种可扩散的分子，在发育过程中参与多种细胞相互作用。BMP4的表达伴随着耳朵感觉器官的发育，在感觉细胞命运的模式化和规范化过程中，但对BMP4在这一过程中的作用还没有了解。本研究旨在探讨骨形态发生蛋白信号对毛细胞发育的影响。为了这个目的，我们研究了基因表达，细胞增殖和细胞死亡分离的鸡耳囊泡，在体外生长的重组骨形态发生蛋白4或骨形态发生蛋白抑制剂头蛋白的存在下。Cath1被用作毛细胞特化的标志物。BMP 4减少了Cathl细胞的数量，相反，Noggin增加了感觉斑的大小和Cathl阳性细胞的数量。BMP 4的作用是不可逆的，发生在毛细胞特化之前。Lfng和Fgf10在前感觉区先于Cath1表达，并且它们的表达被Noggin扩大。在这些阶段，BMP活性的修改没有重新指定的耳泡的非感觉上皮。BMP4可抑制感觉斑BMP4的表达，并可被Noggin诱导，提示存在一个自身调节环。在6和18小时期间BrdU掺入的分析表明，BMP 4的作用是由于其能够减少活跃增殖的祖细胞的数量和抑制细胞命运的规范。骨形态发生蛋白4诱导细胞死亡的前感觉域的耳泡，沿着Msx 1的表达，但不是Msx 2。与此相反，BMP抑制与头蛋白有利于毛细胞的规范没有变化的整体细胞增殖。我们建议，关于终末分裂的阶段，BMP和BMP抑制信号之间的平衡调节毛细胞前体的生存和规范，感觉毛细胞的最终数量受到BMP过量水平的限制。因此，感觉斑的最终大小将取决于BMP 4和相反信号之间的平衡。(c)2006年爱思唯尔公司All rights reserved.
Bone morphogenetic proteins (BMPs) are diffusible molecules involved in a variety of cellular interactions during development. Bmp4 expression accompanies the development of the ear sensory organs during patterning and specification of sensory cell fates, yet there is no understanding of the role of BMP4 in this process. The present work was aimed at exploring the effects of BMP-signaling oil the development of hair-cells. For this purpose, we studied gene expression, cell proliferation and cell death in isolated chick otic vesicles that were grown in vitro in the presence of recombinant BMP4 or the BMP-inhibitor Noggin. Cath1 was used as a marker for hair-cell specification. BMP4 reduced the number of Cathl-cells and, conversely, Noggin increased the size of the sensory patches and the number of Cathl-positive cells. The effect of BMP4 was irreversible and occurred before hair-cell specification. Lfng and Fgf10 were expressed in the prosensory domain before Cath1, and their expression was expanded by Noggin. At these stages, modifications of BMP activity did not respecify non-sensory epithelium of the otic vesicle. The expression of Bmp4 at sensory patches was suppressed by BMP4 and induced by Noggin Suggesting an autoregulatory loop. Analysis of BrdU incorporation during 6 and 18 h indicated that the effects of BMP4 were due to its ability to reduce the number of actively proliferating progenitors and inhibit cell fate specification. BMP4 induced cell death within the prosensory domain of the otic vesicle, along with the expression of Msx1, but not Msx2. On the contrary, BMP-inhibition with Noggin favored hair-cell specification without changes in the overall cell proliferation. We propose that about the stage of terminal division, the balance between BMP and BMP-inhibitory signals regulates survival and specification of hair-cell precursors, the final number of sensory hair-cells being limited by excess levels of BMPs. The final size of sensory patches would hence depend on the balance between BMP4 and opposing signals. (c) 2006 Elsevier Inc. All rights reserved.