Phrenic-specific transcriptional programs shape respiratory motor output
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 ar...
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doaj-8012e740220a4b9193c80bdb0b4cac012021-05-05T20:44:38ZengeLife Sciences Publications LtdeLife2050-084X2020-01-01910.7554/eLife.52859Phrenic-specific transcriptional programs shape respiratory motor outputAlicia N Vagnozzi0https://orcid.org/0000-0002-6152-8728Kiran Garg1Carola Dewitz2Matthew T Moore3Jared M Cregg4https://orcid.org/0000-0002-0027-9748Lucie Jeannotte5Niccolò Zampieri6https://orcid.org/0000-0002-2228-9453Lynn T Landmesser7Polyxeni Philippidou8https://orcid.org/0000-0002-0733-3591Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United StatesDepartment of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United StatesMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, GermanyDepartment of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United StatesDepartment of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United StatesCentre de Recherche sur le Cancer de l'Université Laval, Centre de recherche du CHU de Québec-Université Laval (Oncology), Québec, CanadaMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, GermanyDepartment of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United StatesDepartment of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United StatesThe 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.https://elifesciences.org/articles/52859phrenic motor neuronsHox5 genescadherinsrespirationinhibitionPMC (phrenic motor column) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alicia N Vagnozzi Kiran Garg Carola Dewitz Matthew T Moore Jared M Cregg Lucie Jeannotte Niccolò Zampieri Lynn T Landmesser Polyxeni Philippidou |
spellingShingle |
Alicia N Vagnozzi Kiran Garg Carola Dewitz Matthew T Moore Jared M Cregg Lucie Jeannotte Niccolò Zampieri Lynn T Landmesser Polyxeni Philippidou Phrenic-specific transcriptional programs shape respiratory motor output eLife phrenic motor neurons Hox5 genes cadherins respiration inhibition PMC (phrenic motor column) |
author_facet |
Alicia N Vagnozzi Kiran Garg Carola Dewitz Matthew T Moore Jared M Cregg Lucie Jeannotte Niccolò Zampieri Lynn T Landmesser Polyxeni Philippidou |
author_sort |
Alicia N Vagnozzi |
title |
Phrenic-specific transcriptional programs shape respiratory motor output |
title_short |
Phrenic-specific transcriptional programs shape respiratory motor output |
title_full |
Phrenic-specific transcriptional programs shape respiratory motor output |
title_fullStr |
Phrenic-specific transcriptional programs shape respiratory motor output |
title_full_unstemmed |
Phrenic-specific transcriptional programs shape respiratory motor output |
title_sort |
phrenic-specific transcriptional programs shape respiratory motor output |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2020-01-01 |
description |
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. |
topic |
phrenic motor neurons Hox5 genes cadherins respiration inhibition PMC (phrenic motor column) |
url |
https://elifesciences.org/articles/52859 |
work_keys_str_mv |
AT alicianvagnozzi phrenicspecifictranscriptionalprogramsshaperespiratorymotoroutput AT kirangarg phrenicspecifictranscriptionalprogramsshaperespiratorymotoroutput AT caroladewitz phrenicspecifictranscriptionalprogramsshaperespiratorymotoroutput AT matthewtmoore phrenicspecifictranscriptionalprogramsshaperespiratorymotoroutput AT jaredmcregg phrenicspecifictranscriptionalprogramsshaperespiratorymotoroutput AT luciejeannotte phrenicspecifictranscriptionalprogramsshaperespiratorymotoroutput AT niccolozampieri phrenicspecifictranscriptionalprogramsshaperespiratorymotoroutput AT lynntlandmesser phrenicspecifictranscriptionalprogramsshaperespiratorymotoroutput AT polyxeniphilippidou phrenicspecifictranscriptionalprogramsshaperespiratorymotoroutput |
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