Six1 controls patterning of the mouse otic vesicle
Six1 controls patterning of the mouse otic vesicle
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DOI：
10.1242/dev.00943
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发表时间：
2004-02-01
期刊：
影响因子：
4.6
通讯作者：
Kawakami, K
中科院分区：
文献类型：
--
作者：
Ozaki, H;Nakamura, K;Kawakami, K
Six 1是Six家族同源盒基因的成员，其作为Pax-Six-Eya-Dach基因网络的组成部分起作用以控制器官发育。Six 1在耳泡、鼻上皮、鳃弓/囊、生肾索、体节和有限的神经节中表达。在这项研究中，我们建立了Six 1缺陷小鼠，发现内耳，鼻子，胸腺，肾脏和骨骼肌的发育受到严重影响。6个1基因缺陷胚胎的内耳结构缺失，包括耳蜗和前庭，但其内淋巴囊扩大。内耳异常开始于E10.5左右，Six 1在此阶段野生型胚胎的耳囊腹侧区域表达。在Six 1缺陷胚胎的耳泡中，在野生型耳泡中腹侧表达的Otx 1、Otx 2、Lfng和Fgf 3的表达被取消，而在野生型耳泡中背侧表达的Dlx 5、Hmx 3、Dach 1和Dach 2的表达域腹侧扩展。我们的研究结果表明，Six 1功能作为一个关键的调节耳泡图案在早期胚胎发育和控制下游的耳基因的表达结构域负责各自的内耳结构。此外，细胞增殖减少和凋亡细胞死亡增强腹侧区的耳囊，这表明Six 1参与细胞增殖和生存。尽管Six 1和Shh缺陷小鼠的耳表型相似，但Six 1和Shh的表达相互独立。
Six1 is a member of the Six family homeobox genes, which function as components of the Pax-Six-Eya-Dach gene network to control organ development. Six1 is expressed in otic vesicles, nasal epithelia, branchial arches/pouches, nephrogenic cords, somites and a limited set of ganglia. In this study, we established Six1-deficient mice and found that development of the inner ear, nose, thymus, kidney and skeletal muscle was severely affected. Six1-deficient embryos were devoid of inner ear structures, including cochlea and vestibule, while their endolymphatic sac was enlarged. The inner ear anomaly began at around E10.5 and Six1 was expressed in the ventral region of the otic vesicle in the wild-type embryos at this stage. In the otic vesicle of Six1-deficient embryos, expressions of Otx1, Otx2, Lfng and Fgf3, which were expressed ventrally in the wildtype otic vesicles, were abolished, while the expression domains of Dlx5, Hmx3, Dach1 and Dach2, which were expressed dorsally in the wild-type otic vesicles, expanded ventrally. Our results indicate that Six1 functions as a key regulator of otic vesicle patterning at early embryogenesis and controls the expression domains of downstream otic genes responsible for respective inner ear structures. In addition, cell proliferation was reduced and apoptotic cell death was enhanced in the ventral region of the otic vesicle, suggesting the involvement of Six1 in cell proliferation and survival. In spite of the similarity of otic phenotypes of Six1- and Shh-deficient mice, expressions of Six1 and Shh were mutually independent.