RT Journal Article
SR Electronic
T1 TCF7L2 acts as a molecular switch in midbrain to control mammal vocalization through a transcriptional repression mechanism
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.10.475593
DO 10.1101/2022.01.10.475593
A1 Huihui Qi
A1 Li Luo
A1 Caijing Lu
A1 Runze Chen
A1 Xianyao Zhou
A1 Xiaohui Zhang
A1 Yichang Jia
YR 2022
UL http://biorxiv.org/content/early/2022/01/11/2022.01.10.475593.abstract
AB Vocalization is an essential medium for sexual and social signaling in birds and mammals. Periaqueductal gray (PAG) a conserved midbrain structure is believed to be responsible for innate vocalizations, but its molecular regulation remains largely unknown. Here, through a mouse forward genetic screening we identified one of the key Wnt/ β-catenin effectors TCF7L2/TCF4 controls ultrasonic vocalization (USV) production and syllable complexity during maternal deprivation and sexual encounter. Expression of TCF7L2 in PAG excitatory neurons is necessary for the complex trait, while TCF7L2 loss reduces neuronal gene expressions and synaptic transmission in PAG. TCF7L2-mediated vocal β-catenin-binding domain but dependent of its DNA binding ability. Patient mutations associated with severe speech delay disrupt the transcriptional repression effect of TCF7L2, while mice carrying those mutations display severe USV impairments. Therefore, we conclude that TCF7L2 orchestrates gene expression in midbrain to control vocal production through a transcriptional repression mechanism.Competing Interest StatementThe authors have declared no competing interest.