Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila.
Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila.
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DOI：
10.1534/g3.115.026484
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发表时间：
2016-04-07
期刊：
影响因子：
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通讯作者：
Tomchik SM
中科院分区：
文献类型：
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作者：
King LB;Koch M;Murphy KR;Velazquez Y;Ja WW;Tomchik SM
神经纤维瘤病 I 是一种常见的遗传性疾病，可导致肿瘤形成，并使个体易出现一系列认知/行为症状，包括注意力缺陷、视觉空间技能、学习、语言发育和睡眠以及自闭症谱系障碍样特征。 nf1 编码的神经纤维蛋白 (Nf1) 从普通果蝇、果蝇到人类都表现出高度保守性。果蝇提供了一个强大的平台来研究 Nf1 上游和下游的信号级联，果蝇模型表现出与哺乳动物模型相似的行为表型。为了了解 Nf1 的缺失如何影响果蝇的运动行为，我们将传统的活动监测与梳理行为的视频分析结合起来。在 nf1 突变体中，自发梳理行为增加了 7 倍。这种活性的增加与之前描述的多巴胺依赖性过度活跃不同，因为多巴胺转运蛋白突变体表现出梳理行为略有减少。最后，我们发现可以在测量红外光束中断的标准活动监视器中比较相对梳理频率，从而可以使用活动监视器作为筛选梳理表型的自动化方法。总体而言，这些数据表明，nf1 的缺失会产生过度的活动，表现为修饰增加，从而提供了一个平台来剖析跨神经元回路的神经纤维蛋白信号传导的分子遗传学。
Neurofibromatosis I is a common genetic disorder that results in tumor formation, and predisposes individuals to a range of cognitive/behavioral symptoms, including deficits in attention, visuospatial skills, learning, language development, and sleep, and autism spectrum disorder-like traits. The nf1-encoded neurofibromin protein (Nf1) exhibits high conservation, from the common fruit fly, Drosophila melanogaster, to humans. Drosophila provides a powerful platform to investigate the signaling cascades upstream and downstream of Nf1, and the fly model exhibits similar behavioral phenotypes to mammalian models. In order to understand how loss of Nf1 affects motor behavior in flies, we combined traditional activity monitoring with video analysis of grooming behavior. In nf1 mutants, spontaneous grooming was increased up to 7x. This increase in activity was distinct from previously described dopamine-dependent hyperactivity, as dopamine transporter mutants exhibited slightly decreased grooming. Finally, we found that relative grooming frequencies can be compared in standard activity monitors that measure infrared beam breaks, enabling the use of activity monitors as an automated method to screen for grooming phenotypes. Overall, these data suggest that loss of nf1 produces excessive activity that is manifested as increased grooming, providing a platform to dissect the molecular genetics of neurofibromin signaling across neuronal circuits.