MET Receptor Tyrosine Kinase Regulates Vagal Laryngeal Motor Neuron Development and Lifespan Ultrasonic Vocal Communication

• Published in: bioRxiv
• Main Authors: Kamitakahara, Anna K, Ramin Ali Marandi Ghoddousi, Lanjewar, Alexandra L, Magalong, Valerie M, Wu, Hsiao-Huei, Levitt, Pat
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 15.05.2020
• Subjects: Brain stem; c-Met protein; Embryos; Information processing; Larynx; Life span; Motor neurons; Motor nuclei; Motor task performance; Muscles; Neurons; Nucleus ambiguus; Protein-tyrosine kinase receptors; Vagus nerve; Vocalization behavior
• DOI: 10.1101/2020.05.13.093617

The vagal motor nucleus ambiguus (nAmb) innervates the intrinsic muscles of the larynx, providing direct motor control over vocal production in humans and rodents. Here, we demonstrate that early developmental signaling through the MET receptor tyrosine kinase (MET) is required for proper formation of the nAmb. Embryonic deletion of Met in the developing brainstem resulted in a loss of one-third of motor neurons in the nAmb. While the remaining neurons were able to establish connections with target muscles in the larynx, advanced signal processing analyses revealed severe deficits in ultrasonic vocalization in early postnatal life. Abnormal vocalization patterns persisted into adulthood in the majority of mice tested. Interestingly, 28% of adult mice recovered the ability to vocalize demonstrating heterogeneity in circuit restitution. Together, the data establish MET as a factor necessary for development of a specific subset of neurons in the nAmb required for normal ultrasonic vocalization. Competing Interest Statement The authors have declared no competing interest.