Medical College Reveals the Molecular Basis of Mouse Vocalization
sound can transmit important information, including individual social status, location and experience, and is an important medium for intraspecies communication among birds, rodents, non-human primates and humans. Studying the molecular mechanism of phonation is helpful to better understand the mechanism of the generation and evolution of human language, and it is of great significance to understand the pathogenesis of language dysfunction, autism and other related diseases.
13 February 2023, Tsinghua University School of Medicine, Tsinghua-IDG/McGovern Institute of Brain Science, Tsinghua-Peking University Joint Center for Life Sciences, the research group of Jia Yichang of Brain and Intelligence Laboratory of Tsinghua University published a research paper entitled "Transcription factor TCF7L2 as a molecular switch controls mammalian vocalization in midbrain through DNA binding domain" (TCF7L2 plays a molecular switch role in midbrain and controls mammalian vocalization through its DNA binding domain instead of transcription activation domain) online in the authoritative academic journal Molecular Psychiatry (Molecular Psychiatry) in the field of mental diseases, the molecular basis of mouse vocalization was revealed.
sound requires multiple parts of the body to work together, such as the laryngeal muscles, breathing, and a neural network that spans the forebrain to the brainstem. The periaqueductal gray matter (periaqueductal gray, PAG) is a relatively conserved structure in the brain and is considered to be an important node in the control of congenital vocalization in mice, cats, and non-human primates. As a result, much of the research on phonation revolves around the upstream and downstream neural circuits centered on PAG, however, little is known about the molecular regulatory mechanisms of PAG control of phonation.
Figure 1.TCF7L2 Y337H point mutation impairs mouse vocalization
this study, mouse genes were first mutagenized by the chemical mutagen N-ethyl-N-nitrosourea (N-ethyl-N-nitrosourea, ENU), and then screened for vocalization-deficient mice, it was found thatTcf7l2gene plays a key role in regulating mouse vocalization and affects the syllable complexity of mouse vocalization (Figure 1); brain regions and cell-specific knockoutsTcf7l2impairs vocalization in mice, explainsTcf7l2in excitatory neurons in the PAG brain region is essential for voicing in mice; nanopore sequencing foundTcf7l2, specific knockoutsTcf7l2gene also impair mouse vocalization and are found by the dual luciferase reporter system.Tcf7l2gene uninhibited transcription by short transcripts, suggesting that TCF7L2 may regulate mouse vocalization through transcriptional repression; finally, the researchersTcf7l2gene, introduced into mice, also cause vocal defects in mice.
to sum up, the study from the perspective of molecular genetics, the study ofTcf7l2the mechanism by which mouse vocalization is regulated, the study helps scientists gain insight intoTcf7l2in the nervous system provides a molecular genetic theoretical basis for understanding the phonation mechanism of human language and its related diseases.
Figure 2.Tcf7l2regulation of mouse vocalization
Professor Jia Yichang of Tsinghua University School of Medicine is the corresponding author of this article, Tsinghua University School of Medicine doctoral student Qi Huihui is the first author of this article, Tsinghua University Brain and Intelligence Laboratory teacher Luo Li, Tsinghua University doctoral student Lu Caijing, Chen Runze and Beijing Normal University Zhang Xiaohui team made important contributions to this article. The research work was supported by the National Natural Science Foundation of China, the Tsinghua-Peking University Joint Center for Life Sciences, and the Tsinghua-IDG/McGovern Institute for Brain Science.
Literature Links:https://www.nature.com/articles/s41380-023-01993-5
