Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh
Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh
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DOI：
10.1101/gad.1303905
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发表时间：
2005-07-01
影响因子：
10.5
通讯作者：
Epstein, DJ
中科院分区：
文献类型：
--
作者：
Riccomagno, MM;Takada, S;Epstein, DJ
内耳沿其背侧/腹侧轴沿着被分别划分为前庭器官和听觉器官。基因表达研究表明，这种细分发生在耳泡内，耳泡是所有内耳结构的来源组织。虽然腹侧耳的命运的规格是依赖于从脊索分泌的嘘，负责背侧耳发展的信号的性质还没有被描述。在这项研究中，我们证明，Wnt信号是活跃的耳囊，在那里它的功能来调节前庭形态发生所必需的基因（Dlx 5/6和Gbx 2）的表达的背侧区域。我们进一步表明，Wnt对背耳发育的影响来源于背侧后脑，并确定Wnt 1和Wnt 3a作为该功能所需的特异性配体。Wnt靶基因对背侧耳囊的限制也受到Shh的影响。因此，Wnt和Shh信号活动之间的平衡是区分前庭和听觉细胞类型的关键。
The inner ear is partitioned along its dorsal/ventral axis into vestibular and auditory organs, respectively. Gene expression studies suggest that this subdivision occurs within the otic vesicle, the tissue from which all inner ear structures are derived. While the specification of ventral otic fates is dependent on Shh secreted from the notochord, the nature of the signal responsible for dorsal otic development has not been described. In this study, we demonstrate that Wnt signaling is active in dorsal regions of the otic vesicle, where it functions to regulate the expression of genes (Dlx5/6 and Gbx2) necessary for vestibular morphogenesis. We further show that the source of Wnt impacting on dorsal otic development emanates from the dorsal hindbrain, and identify Wnt1 and Wnt3a as the specific ligands required for this function. The restriction of Wnt target genes to the dorsal otocyst is also influenced by Shh. Thus, a balance between Wnt and Shh signaling activities is key in distinguishing between vestibular and auditory cell types.