Development of the blue cone bipolar cell in the mouse retina

小鼠视网膜中蓝锥双极细胞的发育

• 批准号: 8149214
• 负责人: Wei Li
• 金额: $ 9.36万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8149214
• 关键词: Cells; Development; Mus; Retina; Retinal Cone

Blue cone bipolar cells (blue CBCs) are highly conserved among mammals. Their long, meager dendrites reach for a handful of blue cones and their large axon terminals descend to the bottom of the inner plexiform layer (IPL). In the primate retina, blue CBCs relay the blue-On signals to small bi-stratified ganglion cells, which also receive red/green-Off input and give a blue-On, yellow-Off response. In the mouse retina, a similar type of blue CBC has been identified, which receives inputs from cones that only express blue (S-) opsin. This observed phenomena leads to the questions: how does a blue CBC make such an accurate synaptic connection and do presynaptic cone terminals play an instructive role in the targeting of blue CBCs? In the mouse retina, there is a dorsoventral patterning of M- and S-opsin. M-opsin expression peaks in the dorsal retina and tapers off towards the ventral retina, whereas S-opsin has the opposite pattern. A large proportion of cones in the middle ground express both opsins. The pattern of opsin expression is controlled in early development via thyroid hormone acting at the thyroid hormone receptor 2 (TR2) expressed in cones. In Thrb2-/- (TR2 deficient) mice, M-opsin expression is abolished and all cones become blue cones. We propose to study how the blue CBCs develop facing such a dramatic change in their afferent input in Thrb2-/- mice. We plan to cross the Thrb2-/- mouse line with a transgenic mouse line (Clomeleon-GFP; Clm) in which the blue CBCs (among some other cells) are GFP-labeled and easily recognizable. Currently, we are collecting data from wildtype animals and breeding two mouse lines to obtain heterozygous, and homozygous mice. by analyzing the morphology of blue CBCs in these mice, we will be able to shed light on mechanisms involved in dendritic development and synaptic targeting of blue CBCs.

蓝色锥体双极细胞在哺乳动物中高度保守。它们细长的树突伸向几个蓝色锥体，它们巨大的轴突末端下降到内丛状层(IPL)的底部。在灵长类视网膜中，蓝色CBCs将蓝色开启信号传递给小型双层神经节细胞，后者也接受红色/绿色关闭输入，并给出蓝色开启、黄色关闭的反应。在小鼠的视网膜中，已经发现了一种类似类型的蓝色CBC，它从只表达蓝色(S-)视蛋白的视锥细胞接收输入。这种观察到的现象引出了这样的问题：蓝色CBC是如何建立如此准确的突触连接的，突触前锥体终末在蓝色CBC的靶向中是否起到了指导作用？在小鼠视网膜，有M-和S-视蛋白的背腹图案。M-视蛋白的表达在视网膜背侧最高，向视网膜腹侧逐渐减弱，而S视蛋白的表达模式则相反。中间地面的锥体中有很大一部分同时表达两种视蛋白。视蛋白的表达模式在发育早期是通过甲状腺激素作用于锥体中表达的甲状腺激素受体2(TR2)来控制的。在Thrb2-/-(Tr2缺陷)小鼠中，M-视蛋白表达被取消，所有的视锥细胞都变成了蓝色视锥细胞。我们建议研究在Thrb2-/-小鼠中，面对传入输入的戏剧性变化，蓝色CBCs是如何发展的。我们计划将Thrb2/-小鼠品系与转基因小鼠品系(Clomeleon-GFP；CLM)杂交，在该品系中，蓝色CBCs(在其他一些细胞中)是GFP标记的，易于识别。目前，我们正在收集野生型动物的数据，并培育两个小鼠品系，以获得杂合子和纯合子小鼠。通过分析这些小鼠蓝色CBCs的形态，我们将能够阐明参与蓝色CBCs树突发育和突触靶向的机制。