Phrenic-specific transcriptional programs shape respiratory motor output.

Autor:	Vagnozzi AN; Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United States., Garg K; Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United States., Dewitz C; Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany., Moore MT; Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United States., Cregg JM; Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United States., Jeannotte L; Centre de Recherche sur le Cancer de l'Université Laval, Centre de recherche du CHU de Québec-Université Laval (Oncology), Québec, Canada., Zampieri N; Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany., Landmesser LT; Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United States., Philippidou P; Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 Jan 16; Vol. 9. Date of Electronic Publication: 2020 Jan 16.
DOI:	10.7554/eLife.52859
Abstrakt:	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. Competing Interests: AV, KG, CD, MM, JC, LJ, NZ, LL, PP No competing interests declared (© 2020, Vagnozzi et al.)
Databáze:	MEDLINE
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