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

Frontiers in Neuroscience

Valerie M. Magalong¹  Hsiao-Huei Wu¹  Anna K. Kamitakahara¹  Pat Levitt¹  Alexandra L. Lanjewar²  Ramin Ali Marandi Ghoddousi² 

[1] Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, CA, United States;Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, United States;Program in Developmental Neuroscience and Neurogenetics, Children’s Hospital Los Angeles, The Saban Research Institute, Los Angeles, CA, United States;

关键词: nucleus ambiguus;    ultrasonic vocalization;    MET receptor tyrosine kinase;    vagus;    development;   

DOI  :  10.3389/fnins.2021.768577

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown