Olfactory Sensory Neurons Control Dendritic Complexity of Mitral Cells via Notch Signaling.
Olfactory Sensory Neurons Control Dendritic Complexity of Mitral Cells via Notch Signaling.
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DOI：
10.1371/journal.pgen.1006514
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发表时间：
2016-12
期刊：
影响因子：
4.5
通讯作者：
Saito T
中科院分区：
文献类型：
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作者：
Muroyama Y;Baba A;Kitagawa M;Saito T
哺乳动物嗅球的二尖瓣细胞（MC）具有延伸到单个肾小球的单个初级树突，在那里它们接收来自嗅觉感觉神经元（OSN）的气味信息。控制树突状乔木的MC，在发展过程中动态变化的分子机制，在很大程度上是未知的。在这里，我们发现MCs在Notch信号传导中的关键基因Maml 1的小鼠突变体中显示出更复杂的树突状形态。通过在MC迁移后条件性错误表达MAML 1的显性负性形式（dnMAML 1），观察到类似的表型。相反，Notch的组成性活性形式的条件性错误表达降低了它们的树突复杂性。此外，Notch 1的胞内结构域（NICD 1）定位于MC的核。这些发现表明，Notch信号在胚胎阶段参与树突状复杂的MC。在胚胎期dnMAML 1的错误表达后，许多MCs在出生后阶段异常地将树突延伸到一个以上的肾小球，这表明Notch信号传导对于嗅觉回路的正确形成是必不可少的。此外，在培养的MC树突缩短Jag 1表达细胞。最后，阻断OSN中Notch配体的活性导致树突复杂性的增加以及MC中NICD 1信号的减少。这些结果表明MC的树枝状复杂性由其突触前伙伴OSN控制。嗅觉回路对许多动物的生存至关重要。嗅觉信息由嗅觉神经元传递到中继神经元，中继神经元的形态对信息的处理起着至关重要的作用，并且在物种间具有相似性。哺乳动物的主要中继神经元--僧帽细胞和果蝇的投射神经元在成熟期都只有一个初级树突。控制枝晶形成的分子机制在很大程度上是未知的。MC在发育过程中动态地改变其树突。在这项研究中，我们表明MC的树枝状形态由Notch信号控制，其中许多因素在物种之间非常保守。此外，我们已经发现，在MC中的Notch信号被OSN激活，并且Notch在小鼠嗅觉系统中的中继神经元中起作用，而在果蝇系统中，Notch在OSN中起作用。因此，我们的研究揭示了一个新的步骤，塑造树突状形态的MC。
Mitral cells (MCs) of the mammalian olfactory bulb have a single primary dendrite extending into a single glomerulus, where they receive odor information from olfactory sensory neurons (OSNs). Molecular mechanisms for controlling dendritic arbors of MCs, which dynamically change during development, are largely unknown. Here we found that MCs displayed more complex dendritic morphologies in mouse mutants of Maml1, a crucial gene in Notch signaling. Similar phenotypes were observed by conditionally misexpressing a dominant negative form of MAML1 (dnMAML1) in MCs after their migration. Conversely, conditional misexpression of a constitutively active form of Notch reduced their dendritic complexity. Furthermore, the intracellular domain of Notch1 (NICD1) was localized to nuclei of MCs. These findings suggest that Notch signaling at embryonic stages is involved in the dendritic complexity of MCs. After the embryonic misexpression of dnMAML1, many MCs aberrantly extended dendrites to more than one glomerulus at postnatal stages, suggesting that Notch signaling is essential for proper formation of olfactory circuits. Moreover, dendrites in cultured MCs were shortened by Jag1-expressing cells. Finally, blocking the activity of Notch ligands in OSNs led to an increase in dendritic complexity as well as a decrease in NICD1 signals in MCs. These results demonstrate that the dendritic complexity of MCs is controlled by their presynaptic partners, OSNs. Olfactory circuits are critical for the survival of many animals. Odor information is transmitted from olfactory sensory neurons (OSNs) to relay neurons, the morphology of which is crucial for processing of the information and similar among species. The major relay neurons, mitral cells (MCs) in mammals and projection neurons in flies, have a single primary dendrite at the mature stage. Molecular mechanisms to control the formation of the dendrite are largely unknown. MCs dynamically change their dendrites during development. In this study, we show that the dendritic morphologies of MCs are controlled by Notch signaling, many factors of which are well conserved among species. Moreover, we have found that Notch signaling in MCs is activated by OSNs, and that Notch operates in the relay neurons in the mouse olfactory system, in contrast to the fly system, where Notch functions in OSNs. Therefore, our study has revealed a novel step for shaping the dendritic morphologies of MCs.
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DOI：
10.1523/jneurosci.5746-11.2012
发表时间：
2012-06-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Mizuguchi R;Naritsuka H;Mori K;Mao CA;Klein WH;Yoshihara Y
通讯作者：
Yoshihara Y
影响因子：
46.9
作者：
Nagai, T;Ibata, K;Miyawaki, A
通讯作者：
Miyawaki, A
影响因子：
4.6
作者：
Mizutani, K;Saito, T
通讯作者：
Saito, T
影响因子：
25
作者：
Hoeck, Joerg D.;Jandke, Anett;Behrens, Axel
通讯作者：
Behrens, Axel
DOI：
10.1038/nrg3272
发表时间：
2012-09
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
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