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Phrenic-specific transcriptional programs shape respiratory motor output
eLife ( IF 6.4 ) Pub Date : 2020-01-16
Alicia N Vagnozzi, Kiran Garg, Carola Dewitz, Matthew T Moore, Jared M Cregg, Lucie Jeannotte, Niccolò Zampieri, Lynn T Landmesser, Polyxeni Philippidou

The precise pattern of motor neuron (MN) activation is essential for the execution of motor actions; however, the molecular mechanisms that give rise to specific patterns of MN activity are largely unknown. Phrenic MNs integrate multiple inputs to mediate inspiratory activity during breathing and are constrained to fire in a pattern that drives efficient diaphragm contraction. We show that Hox5 transcription factors shape phrenic MN output by connecting phrenic MNs to inhibitory pre-motor neurons. Hox5 genes establish phrenic MN organization and dendritic topography through the regulation of phrenic-specific cell adhesion programs. In the absence of Hox5 genes, phrenic MN firing becomes asynchronous and erratic due to loss of phrenic MN inhibition. Strikingly, mice lacking Hox5 genes in MNs exhibit abnormal respiratory behavior throughout their lifetime. Our findings support a model where MN-intrinsic transcriptional programs shape the pattern of motor output by orchestrating distinct aspects of MN connectivity.

中文翻译:

ren特异性转录程序影响呼吸运动输出

运动神经元(MN)激活的精确模式对于执行运动动作至关重要。然而,引起MN活动的特定模式的分子机制在很大程度上是未知的。ren性MN集成了多个输入以介导呼吸过程中的吸气活动,并以驱动有效的隔膜收缩的方式约束着火。我们显示Hox5转录因子通过连接MNs抑制前运动神经元塑造shapeMN输出。Hox5基因通过the特异性细胞粘附程序的调节建立establishMN组织和树突状地形。在没有Hox5基因的情况下,由于loss MN抑制的丧失,loss MN的放电变得异步和不稳定。令人惊讶的是,小鼠缺乏MNs中的Hox5基因在其一生中都表现出异常的呼吸行为。我们的发现支持一个模型,其中MN内在的转录程序通过协调MN连接的不同方面来塑造运动输出的模式。
更新日期:2020-01-16
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