Development of the blue cone bipolar cell in the mouse retina

蓝锥双极细胞（Blue CBCs）在哺乳动物中高度保守。它们细长的树突伸向一些蓝色的锥体，它们的大轴突末端伸向内丛状层（IPL）的底部。在灵长类动物的视网膜中，蓝色CBCs将蓝开信号传递给小的双层神经节细胞，后者也接受红/绿关输入，并给出蓝开黄关的反应。在小鼠视网膜中，一种类似的蓝色CBC已经被发现，它接受来自只表达蓝色（S-）视蛋白的视锥细胞的输入。这一观察到的现象引发了以下问题：蓝色CBC是如何建立如此精确的突触连接的？突触前锥体末端在蓝色CBC的靶向中是否发挥了指导作用？在小鼠视网膜中，存在M-视蛋白和s -视蛋白的背腹模式。m -视蛋白的表达在视网膜背侧达到峰值，在视网膜腹侧逐渐减少，而s -视蛋白则具有相反的模式。在中间区域有很大比例的视锥细胞同时表达两种视蛋白。视蛋白的表达模式在发育早期通过甲状腺激素作用于视锥细胞中表达的甲状腺激素受体2 （TR2）而受到控制。在Thrb2-/- （TR2缺陷）小鼠中，M-opsin表达被消除，所有视锥细胞变成蓝色视锥细胞。我们打算研究Thrb2-/-小鼠的传入输入发生如此巨大变化时，蓝色CBCs是如何发育的。我们计划将Thrb2-/-小鼠系与转基因小鼠系（Clomeleon-GFP; Clm）杂交，其中蓝色的CBCs（以及其他一些细胞）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，并培育两种小鼠系，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，我们将能够阐明树突发育和蓝色CBCs突触靶向的机制。

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.