Requirement for Lmo4 in the vestibular morphogenesis of mouse inner ear.
Requirement for Lmo4 in the vestibular morphogenesis of mouse inner ear.
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DOI：
10.1016/j.ydbio.2009.11.003
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发表时间：
2010-02-01
影响因子：
2.7
通讯作者：
Gan, Lin
中科院分区：
文献类型：
--
作者：
Deng, Min;Pan, Ling;Xie, Xiaoling;Gan, Lin
在发育过程中，早期胚胎结构的区室化产生了具有不同特性和发育潜力的细胞块。脊椎动物内耳的听觉和前庭组成部分是在胚胎发育过程中从耳囊内定义的隔室中衍生出来的。前庭器官包括三个半规管、球囊、椭圆囊及其相关的感觉器官，检测头部的角加速度和线加速度，并通过前庭神经元将信息中继到脑干中的前庭核。早期发育事件如何在分子水平上表现前庭结构在很大程度上是未知的。在这里，我们表明，LMO 4，一个LIM域的转录调节，是需要半规管和相关的感觉嵴的形成。有针对性地破坏Lmo4导致前庭的畸形，并且没有三个半规管，前嵴和后嵴。在Lmo4无效的耳囊肿，运河outpouches未能形成和细胞增殖减少在背外侧区域。已知的耳标志物的表达分析表明，Lmo4是必不可少的Bmp4，Fgf10，Msx1，Isl1，Gata3，和Dlx5的正常表达在耳囊的背外侧域，而最初的划分的耳囊保持不受影响。我们的研究结果表明，Lmo4通过两种不同的机制来控制背外侧耳囊肿发育为半规管和嵴：调节耳特异性基因的表达和刺激耳囊肿背外侧部分的增殖。
During development, compartmentalization of an early embryonic structure produces blocks of cells with distinct properties and developmental potentials. The auditory and vestibular components of vertebrate inner ears are derived from defined compartments within the otocyst during embryogenesis. The vestibular apparatus, including three semicircular canals, saccule, utricle, and their associated sensory organs, detects angular and linear acceleration of the head and relays the information through vestibular neurons to vestibular nuclei in the brainstem. How the early developmental events manifest vestibular structures at the molecular level is largely unknown. Here, we show that LMO4, a LIM-domain-only transcriptional regulator, is required for the formation of semicircular canals and their associated sensory cristae. Targeted disruption of Lmo4 resulted in the dysmorphogenesis of the vestibule and in the absence of three semicircular canals, anterior and posterior cristae. In Lmo4-null otocysts, canal outpouches failed to form and cell proliferation was reduced in the dorsolateral region. Expression analysis of the known otic markers showed that Lmo4 is essential for the normal expression of Bmp4, Fgf10, Msx1, Isl1, Gata3, and Dlx5 in the dorsolateral domain of the otocyst, whereas the initial compartmentalization of the otocyst remains unaffected. Our results demonstrate that Lmo4 controls the development of the dorsolateral otocyst into semicircular canals and cristae through two distinct mechanisms: regulating the expression of otic specific genes and stimulating the proliferation of the dorsolateral part of the otocyst.
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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。
影响因子：
4.5
作者：
Chang, Weise;Lin, Zhengshi;Kulessa, Holger;Hebert, Jean;Hogan, Brigid L. M.;Wu, Doris K.
通讯作者：
Wu, Doris K.
影响因子：
4.6
作者：
Alvarez, Y;Alonso, MT;Schimmang, T
通讯作者：
Schimmang, T
影响因子：
5.3
作者：
Hahm, KM;Sum, EYM;Orkin, SH
通讯作者：
Orkin, SH
影响因子：
2.7
作者：
Gan, L;Wang, SW;Klein, WH
通讯作者：
Klein, WH
影响因子：
2.7
作者：
Auerbach, W;Dunmore, JH;Joyner, AL
通讯作者：
Joyner, AL