Phrenic-specific transcriptional programs shape respiratory motor output
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Phrenic-specific transcriptional programs shape respiratory motor output. / Vagnozzi, Alicia N; Garg, Kiran; Dewitz, Carola; Moore, Matthew T; Cregg, Jared M; Jeannotte, Lucie; Zampieri, Niccolò; Landmesser, Lynn T; Philippidou, Polyxeni.
In: eLife, Vol. 9, e52859, 16.01.2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Phrenic-specific transcriptional programs shape respiratory motor output
AU - Vagnozzi, Alicia N
AU - Garg, Kiran
AU - Dewitz, Carola
AU - Moore, Matthew T
AU - Cregg, Jared M
AU - Jeannotte, Lucie
AU - Zampieri, Niccolò
AU - Landmesser, Lynn T
AU - Philippidou, Polyxeni
N1 - © 2020, Vagnozzi et al.
PY - 2020/1/16
Y1 - 2020/1/16
N2 - 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 premotor 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.
AB - 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 premotor 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.
U2 - 10.7554/eLife.52859
DO - 10.7554/eLife.52859
M3 - Journal article
C2 - 31944180
VL - 9
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e52859
ER -
ID: 248113721