Evolution of Osteocrin as an activity-regulated factor in the primate brain.
Evolution of Osteocrin as an activity-regulated factor in the primate brain.
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DOI：
10.1038/nature20111
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发表时间：
2016-11-10
期刊：
影响因子：
64.8
通讯作者：
Greenberg ME
中科院分区：
文献类型：
--
作者：
Ataman B;Boulting GL;Harmin DA;Yang MG;Baker-Salisbury M;Yap EL;Malik AN;Mei K;Rubin AA;Spiegel I;Durresi E;Sharma N;Hu LS;Pletikos M;Griffith EC;Partlow JN;Stevens CR;Adli M;Chahrour M;Sestan N;Walsh CA;Berezovskii VK;Livingstone MS;Greenberg ME
感觉刺激部分通过激活调节突触发育和可塑性的基因表达网络来驱动哺乳动物神经系统的成熟和功能。这些网络主要在小鼠中进行了研究，目前尚不清楚是否有物种或分支特异性活性调节基因控制大脑发育和功能的特征。在这里，我们使用人胎脑培养物的转录谱，以确定一个活动依赖性分泌因子，骨蛋白（Osteocrin），这是由人，但不是小鼠神经元的膜去极化诱导。我们发现，通过进化获得结合活性调节转录因子MEF2的DNA调控元件，ODN已在灵长类动物中被重新利用。此外，我们还证明了Ostroma在灵长类动物新皮层中表达，并限制了人类神经元中活性依赖性树突状细胞的生长。这些发现表明，在对感觉输入的反应中，ODN调节灵长类动物特有的神经元结构和功能的特征。
Sensory stimuli drive the maturation and function of the mammalian nervous system in part through the activation of gene expression networks that regulate synapse development and plasticity. These networks have primarily been studied in mice, and it is not known whether there are species- or clade-specific activity-regulated genes that control features of brain development and function. Here we use transcriptional profiling of human fetal brain cultures to identify an activity-dependent secreted factor, Osteocrin (OSTN), that is induced by membrane depolarization of human but not mouse neurons. We find that OSTN has been repurposed in primates through the evolutionary acquisition of DNA regulatory elements that bind the activity-regulated transcription factor MEF2. In addition, we demonstrate that OSTN is expressed in primate neocortex and restricts activity-dependent dendritic growth in human neurons. These findings suggest that, in response to sensory input, OSTN regulates features of neuronal structure and function that are unique to primates.