Requirement of adenylate cyclase 1 for the ephrin-A5-dependent retraction of exuberant retinal axons
Requirement of adenylate cyclase 1 for the ephrin-A5-dependent retraction of exuberant retinal axons
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DOI：
10.1523/jneurosci.3385-05.2006
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发表时间：
2006-01-18
影响因子：
5.3
通讯作者：
Gaspar, P
中科院分区：
文献类型：
--
作者：
Nicol, X;Muzerelle, A;Gaspar, P
钙刺激腺苷酸环化酶 1 (AC1) 已被证明是细化视网膜专题图所必需的，但所涉及的机制尚不清楚。为了研究这个问题，我们设计了一种视网膜顶盖共培养制剂，可重现沿着上丘（SC）的头尾轴逐渐获得的地形特异性。体外 (DIV) 4 天时，颞部视网膜轴突侵入整个 SC，并在 12 DIV 时消除尾部旺盛的分支。颞轴和鼻轴突分别优先在喙侧或尾侧 SC 中形成分支。 AC1 缺陷小鼠的视网膜外植体 AC1(brl/brl) 在遇到野生型 (WT) SC 时保持旺盛的分支并失去分支的区域选择性。相反，WT 视网膜正确靶向 AC1(brl/brl) 丘脑外植体。 WT 共培养物中肝配蛋白-A5 信号传导的阻断模仿了视网膜中 AC1 功能丧失的影响。视频显微分析表明，AC1(brl/brl) 轴突对肝配蛋白 A5 的反应发生了改变：发生生长锥的塌陷，但轴突的向后运动被阻止。我们的结果证明了 AC1 在视网膜中的突触前细胞自主作用，并进一步表明，在视网膜专题图的细化过程中，AC1 对于视网膜轴突对 ephrin-A5 的回缩反应是必要的。
The calcium-stimulated adenylate cyclase 1 (AC1) has been shown to be required for the refinement of the retinotopic map, but the mechanisms involved are not known. To investigate this question, we devised a retinotectal coculture preparation that reproduces the gradual acquisition of topographic specificity along the rostrocaudal axis of the superior colliculus (SC). Temporal retinal axons invade the entire SC at 4 d in vitro (DIV) and eliminate exuberant branches caudally by 12 DIV. Temporal and nasal axons form branches preferentially in the rostral or caudal SC, respectively. Retinal explants from AC1-deficient mice, AC1(brl/brl), maintain exuberant branches and lose the regional selectivity of branching when confronted with wild-type (WT) SC. Conversely, WT retinas correctly target AC1(brl/brl) collicular explants. The effects of AC1 loss of function in the retina are mimicked by the blockade of ephrin-A5 signaling in WT cocultures. Video microscopic analyses show that AC1(brl/brl) axons have modified responses to ephrin- A5: the collapse of the growth cones occurs, but the rearward movement of the axon is arrested. Our results demonstrate a presynaptic, cell autonomous role of AC1 in the retina and further indicate that AC1 is necessary to enact a retraction response of the retinal axons to ephrin- A5 during the refinement of the retinotopic map.