Phrenic-specific transcriptional programs shape respiratory motor output
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- Phrenic-specific transcriptional programs shape respiratory motor output_(publisher_version)
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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.
Original language | English |
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Article number | e52859 |
Journal | eLife |
Volume | 9 |
ISSN | 2050-084X |
DOIs | |
Publication status | Published - 16 Jan 2020 |
Externally published | Yes |
Bibliographical note
© 2020, Vagnozzi et al.
ID: 248113721