MET Receptor Tyrosine Kinase Regulates Lifespan Ultrasonic Vocalization and Vagal Motor Neuron Development

The intrinsic muscles of the larynx are innervated by the vagal motor nucleus ambiguus (nAmb), which provides direct motor control over vocal production in humans and rodents. Here, we demonstrate in mice using the Phox2bCre line, that conditional embryonic deletion of the gene encoding the MET rece...

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Autores principales:	Anna K. Kamitakahara, Ramin Ali Marandi Ghoddousi, Alexandra L. Lanjewar, Valerie M. Magalong, Hsiao-Huei Wu, Pat Levitt
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	nucleus ambiguus ultrasonic vocalization MET receptor tyrosine kinase vagus development Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/b69dde39302d4c56b375040d00453975
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id	oai:doaj.org-article:b69dde39302d4c56b375040d00453975
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spelling	oai:doaj.org-article:b69dde39302d4c56b375040d004539752021-11-04T08:50:24ZMET Receptor Tyrosine Kinase Regulates Lifespan Ultrasonic Vocalization and Vagal Motor Neuron Development1662-453X10.3389/fnins.2021.768577https://doaj.org/article/b69dde39302d4c56b375040d004539752021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.768577/fullhttps://doaj.org/toc/1662-453XThe intrinsic muscles of the larynx are innervated by the vagal motor nucleus ambiguus (nAmb), which provides direct motor control over vocal production in humans and rodents. Here, we demonstrate in mice using the Phox2bCre line, that conditional embryonic deletion of the gene encoding the MET receptor tyrosine kinase (MET) in the developing brainstem (cKO) results in highly penetrant, severe deficits in ultrasonic vocalization in early postnatal life. Major deficits and abnormal vocalization patterns persist into adulthood in more than 70% of mice, with the remaining recovering the ability to vocalize, reflecting heterogeneity in circuit restitution. We show that underlying the functional deficits, conditional deletion of Met results in a loss of approximately one-third of MET+ nAmb motor neurons, which begins as early as embryonic day 14.5. The loss of motor neurons is specific to the nAmb, as other brainstem motor and sensory nuclei are unaffected. In the recurrent laryngeal nerve, through which nAmb motor neurons project to innervate the larynx, there is a one-third loss of axons in cKO mice. Together, the data reveal a novel, heterogenous MET-dependence, for which MET differentially affects survival of a subset of nAmb motor neurons necessary for lifespan ultrasonic vocal capacity.Anna K. KamitakaharaAnna K. KamitakaharaRamin Ali Marandi GhoddousiRamin Ali Marandi GhoddousiRamin Ali Marandi GhoddousiAlexandra L. LanjewarAlexandra L. LanjewarAlexandra L. LanjewarValerie M. MagalongValerie M. MagalongHsiao-Huei WuPat LevittPat LevittFrontiers Media S.A.articlenucleus ambiguusultrasonic vocalizationMET receptor tyrosine kinasevagusdevelopmentNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nucleus ambiguus ultrasonic vocalization MET receptor tyrosine kinase vagus development Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	nucleus ambiguus ultrasonic vocalization MET receptor tyrosine kinase vagus development Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Anna K. Kamitakahara Anna K. Kamitakahara Ramin Ali Marandi Ghoddousi Ramin Ali Marandi Ghoddousi Ramin Ali Marandi Ghoddousi Alexandra L. Lanjewar Alexandra L. Lanjewar Alexandra L. Lanjewar Valerie M. Magalong Valerie M. Magalong Hsiao-Huei Wu Pat Levitt Pat Levitt MET Receptor Tyrosine Kinase Regulates Lifespan Ultrasonic Vocalization and Vagal Motor Neuron Development
description	The intrinsic muscles of the larynx are innervated by the vagal motor nucleus ambiguus (nAmb), which provides direct motor control over vocal production in humans and rodents. Here, we demonstrate in mice using the Phox2bCre line, that conditional embryonic deletion of the gene encoding the MET receptor tyrosine kinase (MET) in the developing brainstem (cKO) results in highly penetrant, severe deficits in ultrasonic vocalization in early postnatal life. Major deficits and abnormal vocalization patterns persist into adulthood in more than 70% of mice, with the remaining recovering the ability to vocalize, reflecting heterogeneity in circuit restitution. We show that underlying the functional deficits, conditional deletion of Met results in a loss of approximately one-third of MET+ nAmb motor neurons, which begins as early as embryonic day 14.5. The loss of motor neurons is specific to the nAmb, as other brainstem motor and sensory nuclei are unaffected. In the recurrent laryngeal nerve, through which nAmb motor neurons project to innervate the larynx, there is a one-third loss of axons in cKO mice. Together, the data reveal a novel, heterogenous MET-dependence, for which MET differentially affects survival of a subset of nAmb motor neurons necessary for lifespan ultrasonic vocal capacity.
format	article
author	Anna K. Kamitakahara Anna K. Kamitakahara Ramin Ali Marandi Ghoddousi Ramin Ali Marandi Ghoddousi Ramin Ali Marandi Ghoddousi Alexandra L. Lanjewar Alexandra L. Lanjewar Alexandra L. Lanjewar Valerie M. Magalong Valerie M. Magalong Hsiao-Huei Wu Pat Levitt Pat Levitt
author_facet	Anna K. Kamitakahara Anna K. Kamitakahara Ramin Ali Marandi Ghoddousi Ramin Ali Marandi Ghoddousi Ramin Ali Marandi Ghoddousi Alexandra L. Lanjewar Alexandra L. Lanjewar Alexandra L. Lanjewar Valerie M. Magalong Valerie M. Magalong Hsiao-Huei Wu Pat Levitt Pat Levitt
author_sort	Anna K. Kamitakahara
title	MET Receptor Tyrosine Kinase Regulates Lifespan Ultrasonic Vocalization and Vagal Motor Neuron Development
title_short	MET Receptor Tyrosine Kinase Regulates Lifespan Ultrasonic Vocalization and Vagal Motor Neuron Development
title_full	MET Receptor Tyrosine Kinase Regulates Lifespan Ultrasonic Vocalization and Vagal Motor Neuron Development
title_fullStr	MET Receptor Tyrosine Kinase Regulates Lifespan Ultrasonic Vocalization and Vagal Motor Neuron Development
title_full_unstemmed	MET Receptor Tyrosine Kinase Regulates Lifespan Ultrasonic Vocalization and Vagal Motor Neuron Development
title_sort	met receptor tyrosine kinase regulates lifespan ultrasonic vocalization and vagal motor neuron development
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/b69dde39302d4c56b375040d00453975
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MET Receptor Tyrosine Kinase Regulates Lifespan Ultrasonic Vocalization and Vagal Motor Neuron Development

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