Bmp4 is essential for the formation of the vestibular apparatus that detects angular head movements.
Bmp4 is essential for the formation of the vestibular apparatus that detects angular head movements.
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BMP4对于检测角头运动的前庭设备的形成至关重要。
DOI：
10.1371/journal.pgen.1000050
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发表时间：
2008-04-11
期刊：
影响因子：
4.5
通讯作者：
Wu, Doris K.
中科院分区：
文献类型：
--
作者：
Chang, Weise;Lin, Zhengshi;Kulessa, Holger;Hebert, Jean;Hogan, Brigid L. M.;Wu, Doris K.
脊椎动物头部的角度运动是由内耳的三个半规管及其相关的感觉组织嵴检测的。骨形态发生蛋白4（Bmp 4）是转化生长因子β（TGF-β）家族的一员，在斑马鱼、青蛙、鸡和小鼠等多种动物的嵴发育过程中保守表达。使用小鼠模型，其中BMP 4是有条件地删除内耳，以及鸡模型中，BMP信号被敲低，特别是在嵴，我们表明，BMP 4是必不可少的形成所有三个嵴及其相关的运河。我们的研究结果表明，Bmp 4不介导的感觉毛和嵴内的支持细胞的形成，通过直接调节所需的内耳，如Serrate 1（锯齿状1在小鼠），Fgf 10和Sox 2的前感觉发育的基因。相反，Bmp 4最有可能通过调节感觉区中的Lmo 4和Msx 1以及嵴的非感觉区（即交叉隔）中的Gata 3、p75 Ngfr和Lmo 4来介导嵴的形成。在根管内，Bmp 2和Dlx 5直接或间接受Bmp 4的调节。脊椎动物内耳感觉器官的形成机制被认为类似于果蝇中调节感觉刚毛形成的机制。我们的研究结果表明，在比较感觉刚毛，在内耳嵴的形成需要一个额外的步骤的感觉和非感觉的命运规范。平衡感的破坏是高度衰弱的，导致眩晕和恶心。保持适当的平衡需要来自身体许多部位的感觉输入，包括内耳和眼睛。在内耳内，前庭器官在平衡感中起着关键作用，并负责检测头部方向和运动。前庭器官检测头部角度运动的部分由三个充满液体的半规管组成，它们彼此成直角。在每根神经管的一端是一个扩大的部分，其中容纳了感觉组织壶腹嵴，由感觉毛细胞和支持细胞组成。骨形态发生蛋白4（Bmp 4），一种分泌的信号分子，在发育过程中在这些感觉区域表达。然而，小鼠中Bmp 4的缺乏不仅影响感觉区域的形成，还影响其相关通道的形成。这些结果第一次证明，一个单一的基因，Bmp 4，是需要形成整个感觉器官，以检测头部的角度运动。
Angular head movements in vertebrates are detected by the three semicircular canals of the inner ear and their associated sensory tissues, the cristae. Bone morphogenetic protein 4 (Bmp4), a member of the Transforming growth factor family (TGF-β), is conservatively expressed in the developing cristae in several species, including zebrafish, frog, chicken, and mouse. Using mouse models in which Bmp4 is conditionally deleted within the inner ear, as well as chicken models in which Bmp signaling is knocked down specifically in the cristae, we show that Bmp4 is essential for the formation of all three cristae and their associated canals. Our results indicate that Bmp4 does not mediate the formation of sensory hair and supporting cells within the cristae by directly regulating genes required for prosensory development in the inner ear such as Serrate1 (Jagged1 in mouse), Fgf10, and Sox2. Instead, Bmp4 most likely mediates crista formation by regulating Lmo4 and Msx1 in the sensory region and Gata3, p75Ngfr, and Lmo4 in the non-sensory region of the crista, the septum cruciatum. In the canals, Bmp2 and Dlx5 are regulated by Bmp4, either directly or indirectly. Mechanisms involved in the formation of sensory organs of the vertebrate inner ear are thought to be analogous to those regulating sensory bristle formation in Drosophila. Our results suggest that, in comparison to sensory bristles, crista formation within the inner ear requires an additional step of sensory and non-sensory fate specification. Disruption of the sense of balance is highly debilitating, causing vertigo and nausea. Maintenance of proper balance requires sensory inputs from many body parts, including the inner ears and the eyes. Within the inner ear, the vestibular apparatus plays a key role in the sense of balance and is responsible for detecting head orientation and movements. The portion of the vestibular apparatus that detects angular head movements consists of three fluid-filled, semicircular canals oriented at right angles to each other. At one end of each canal is an enlargement that houses the sensory tissue, crista ampullaris, consisting of sensory hair cells and supporting cells. Bone morphogenetic protein 4 (Bmp4), a secreted signaling molecule, is expressed in these sensory regions during development. However, the lack of Bmp4 in mice affects the formation of not only the sensory regions but also their associated canals. These results demonstrate for the first time that a single gene, Bmp4, is required for the formation of the entire sensory apparatus for detecting angular head movements.
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影响因子：
2.7
作者：
Alsina, B;Abelló, G;Giraldez, F
通讯作者：
Giraldez, F
影响因子：
2.7
作者：
Chang, WS;Nunes, FD;Wu, DK
通讯作者：
Wu, DK
影响因子：
4.6
作者：
Chang, W;Brigande, JV;Wu, DK
通讯作者：
Wu, DK
影响因子：
4.6
作者：
Brooker, R;Hozumi, K;Lewis, J
通讯作者：
Lewis, J
DOI：
10.1073/pnas.97.22.11692
发表时间：
2000-10-24
影响因子：
11.1
作者：
Eddison, M;Le Roux, I;Lewis, J
通讯作者：
Lewis, J