Cross-repressive interactions between Lrig3 and netrin 1 shape the architecture of the inner ear.
Cross-repressive interactions between Lrig3 and netrin 1 shape the architecture of the inner ear.
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DOI：
10.1242/dev.029330
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Goodrich LV
中科院分区：
文献类型：
--
作者：
Abraira VE;Del Rio T;Tucker AF;Slonimsky J;Keirnes HL;Goodrich LV
平衡感取决于内耳的复杂结构，内耳包含三个半规管，用于检测头部在空间中的运动。即使是一个管道形状的变化也会导致严重的行为缺陷，这突出了了解确保这种精确结构完美形成的细胞和分子事件的必要性。在发育过程中，耳道是从一个简单的上皮球（耳泡）中长出来的小袋中雕刻出来的。一个关键事件是两个相对的上皮细胞壁在每个囊的中心融合，从而产生一个中空的管道。在基因陷阱诱变筛选过程中，我们发现，IG超家族蛋白Lrig 3是侧管发育所必需的。我们表明，这种表型是由于异位表达的轴突导向分子Netrin 1（Ntn 1），它调节基底层的完整性融合板。通过一系列的遗传实验，我们表明，Lrig 3和Ntn 1之间的相互拮抗的相互作用，创造互补的表达结构域，定义未来的形状的侧管。值得注意的是，从Lrig 3突变体中去除一个Ntn 1拷贝可以挽救盘旋行为和运河畸形。因此，Lrig 3/Ntn 1反馈回路决定了在运河发展过程中何时何地发生基底膜破裂，揭示了复杂组织形态发生的新机制。
The sense of balance depends on the intricate architecture of the inner ear, which contains three semicircular canals used to detect motion of the head in space. Changes in the shape of even one canal cause drastic behavioral deficits, highlighting the need to understand the cellular and molecular events that ensure perfect formation of this precise structure. During development, the canals are sculpted from pouches that grow out of a simple ball of epithelium, the otic vesicle. A key event is the fusion of two opposing epithelial walls in the center of each pouch, thereby creating a hollow canal. During the course of a gene trap mutagenesis screen to find new genes required for canal morphogenesis, we discovered that the Ig superfamily protein Lrig3 is necessary for lateral canal development. We show that this phenotype is due to ectopic expression of the axon guidance molecule Netrin1 (Ntn1), which regulates basal lamina integrity in the fusion plate. Through a series of genetic experiments, we show that mutually antagonistic interactions between Lrig3 and Ntn1 create complementary expression domains that define the future shape of the lateral canal. Remarkably, removal of one copy of Ntn1 from Lrig3 mutants rescues both the circling behavior and the canal malformation. Thus, the Lrig3/Ntn1 feedback loop dictates when and where basement membrane breakdown occurs during canal development, revealing a new mechanism of complex tissue morphogenesis.
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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：
3.1
作者：
Ljuslinder, Ingrid;Golovleva, Irina;Malmer, Beatrice
通讯作者：
Malmer, Beatrice
DOI：
10.1007/978-0-387-76715-4_2
发表时间：
2007-01-01
期刊：
AXON GROWTH AND GUIDANCE
影响因子：
--
作者：
Moore, Simon W.;Tessier-Lavigne, Marc;Kennedy, Timothy E.
通讯作者：
Kennedy, Timothy E.
影响因子：
11.4
作者：
Gur, G;Rubin, C;Yarden, Y
通讯作者：
Yarden, Y
影响因子：
12.7
作者：
Guo, DS;Nilsson, J;Henriksson, R
通讯作者：
Henriksson, R