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Phrenic-specific transcriptional programs shape respiratory motor output

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Item Type:Article
Title:Phrenic-specific transcriptional programs shape respiratory motor output
Creators Name:Vagnozzi, A.N. and Garg, K. and Dewitz, C. and Moore, M.T. and Cregg, J.M. and Jeannotte, L. and Zampieri, N. and Landmesser, L.T. and Philippidou, P.
Abstract: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. genes establish phrenic MN organization and dendritic topography through the regulation of phrenic-specific cell adhesion programs. In the absence of genes, phrenic MN firing becomes asynchronous and erratic due to loss of phrenic MN inhibition. Strikingly, mice lacking 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.
Keywords:PMC, Phrenic Motor Neurons,, Hox5 Genes, Cadherins, Respiration, Inhibition
Publisher:eLife Sciences Publications
Page Range:e52859
Date:16 January 2020
Official Publication:https://doi.org/10.7554/eLife.52859
PubMed:View item in PubMed

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