Semicircular canal morphogenesis in the zebrafish inner ear requires the function of gpr126 (lauscher), an adhesion class G protein-coupled receptor gene.
Semicircular canal morphogenesis in the zebrafish inner ear requires the function of gpr126 (lauscher), an adhesion class G protein-coupled receptor gene.
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DOI：
10.1242/dev.098061
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发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
Whitfield TT
中科院分区：
文献类型：
--
作者：
Geng FS;Abbas L;Baxendale S;Holdsworth CJ;Swanson AG;Slanchev K;Hammerschmidt M;Topczewski J;Whitfield TT
脊椎动物内耳中半规管导管的形态发生是胚胎中上皮重塑的一个戏剧性的例子，而正常导管发育的失败会导致前庭功能障碍。在斑马鱼和非洲爪哇中，当上皮的突起在细胞外基质的驱动下进入耳囊并融合形成柱状物时，半规管导管就会形成。我们发现在斑马鱼中，细胞外基质基因在投影生长过程中高表达，然后在融合后迅速下调。酶作用破坏了突起中的透明质酸，导致突起坍塌，无法形成立柱：结果，耳朵肿胀。我们克隆了一个斑马鱼突变体Lauscher(Lau)，通过其肿胀的耳朵表型进行了鉴定。耳部的主要缺陷是畸形的突起和融合不能形成半规管柱状物。细胞外基质成分的基因表达受到高度干扰：几个基因未能下调，并在幼虫后期保持异常高水平的表达。LAU突变破坏了黏附G类蛋白偶联受体基因GPR126。GPR126的表达类似于耳朵和神经脊标记Sox10的表达，并部分依赖于Sox10的活性。CAMP激动剂可以恢复低构型LAU等位基因中管状投射的融合和耳道VERSICA表达的下调。我们认为，GPR126通过cAMP介导的途径，通过调节细胞外基质基因的表达来控制斑马鱼耳部管状突起的生长和黏附。
Morphogenesis of the semicircular canal ducts in the vertebrate inner ear is a dramatic example of epithelial remodelling in the embryo, and failure of normal canal development results in vestibular dysfunction. In zebrafish and Xenopus, semicircular canal ducts develop when projections of epithelium, driven by extracellular matrix production, push into the otic vesicle and fuse to form pillars. We show that in the zebrafish, extracellular matrix gene expression is high during projection outgrowth and then rapidly downregulated after fusion. Enzymatic disruption of hyaluronan in the projections leads to their collapse and a failure to form pillars: as a result, the ears swell. We have cloned a zebrafish mutant, lauscher (lau), identified by its swollen ear phenotype. The primary defect in the ear is abnormal projection outgrowth and a failure of fusion to form the semicircular canal pillars. Otic expression of extracellular matrix components is highly disrupted: several genes fail to become downregulated and remain expressed at abnormally high levels into late larval stages. The lau mutations disrupt gpr126, an adhesion class G protein-coupled receptor gene. Expression of gpr126 is similar to that of sox10, an ear and neural crest marker, and is partially dependent on sox10 activity. Fusion of canal projections and downregulation of otic versican expression in a hypomorphic lau allele can be restored by cAMP agonists. We propose that Gpr126 acts through a cAMP-mediated pathway to control the outgrowth and adhesion of canal projections in the zebrafish ear via the regulation of extracellular matrix gene expression.
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DOI：
10.1242/dev.029330
发表时间：
2008-12
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Abraira VE;Del Rio T;Tucker AF;Slonimsky J;Keirnes HL;Goodrich LV
通讯作者：
Goodrich LV
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：
Cecconi, F;Roth, KA;Salminen, M
通讯作者：
Salminen, M
影响因子：
2.7
作者：
Chiang, EFL;Pai, CI;Chung, BC
通讯作者：
Chung, BC
影响因子：
6.2
作者：
Brösamle, C;Halpern, ME
通讯作者：
Halpern, ME