TCF7L2 acts as a molecular switch in midbrain to control mammal vocalization through a transcriptional repression mechanism

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 control is independent of its 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.

Download Full-text

Multi-breed Genetic Parameters and Genome-wide Association Studies for Mortality Rate at Birth in Pigs

10.21203/rs.3.rs-146253/v1 ◽

2021 ◽

Author(s):

Meijing An ◽

Guangliang Zhou ◽

Yang Li ◽

Tao Xiang ◽

Yunlong Ma ◽

...

Keyword(s):

Mortality Rate ◽

Genetic Parameters ◽

Association Studies ◽

Genetic Correlations ◽

Complex Trait ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Gene Expressions ◽

Genome Wide ◽

Piglet Mortality

Abstract Background Piglet mortality is an economically important complex trait that impacts sow prolificacy in the pig industry. The genetic parameters estimations and genome-wide association studies will help us to better understand the genetic fundamentals of piglet mortality. However, compared with other economically important traits, a little breakthrough in the genetic analyses of the trait has been achieved. Results In this study, we used multi-breed data sets from Yorkshire, Landrace, and Duroc sows and characterized the genetic and genomic properties of mortality rate at birth by treating each parity as a different trait. The heritability of mortality rate from parity I to III were estimated to be 0.0630, 0.1031, and 0.1140, respectively. The phenotypic and genetic correlations with its component traits were all positive with ranges from 0.0897 to 0.9054, and 0.2388 to 0.9999, respectively. Integrating the results, we identified 21 loci that were detected at least by two tools from standard MLM, FarmCPU, BLINK and mrMLM, and these loci were annotated to 22 genes. The annotations revealed that the gene expressions were associated with the reproductive system, nervous system, digestive system, and embryonic development, which are reasonably related to the piglet mortality. Conclusions In brief, the genetic properties of piglet mortality at birth were reported. These findings are expected to provide much information for understanding the genetic and genomic fundamentals of farrowing mortality and also identify candidate molecular markers for breeding practice.

Download Full-text

Cooperative vocal control in marmoset monkeys via vocal feedback

Journal of Neurophysiology ◽

10.1152/jn.00228.2015 ◽

2015 ◽

Vol 114 (1) ◽

pp. 274-283 ◽

Cited By ~ 29

Author(s):

Jung Yoon Choi ◽

Daniel Y. Takahashi ◽

Asif A. Ghazanfar

Keyword(s):

Sound Intensity ◽

Dynamic Interactions ◽

Response Latencies ◽

Vocal Production ◽

Vocal Responses ◽

Vocal Control ◽

Contact Calls ◽

Drive Systems ◽

High Level ◽

Marmoset Monkeys

Humans adjust speech amplitude as a function of distance from a listener; we do so in a manner that would compensate for such distance. This ability is presumed to be the product of high-level sociocognitive skills. Nonhuman primates are thought to lack such socially related flexibility in vocal production. Using predictions from a simple arousal-based model whereby vocal feedback from a conspecific modulates the drive to produce a vocalization, we tested whether another primate exhibits this type of cooperative vocal control. We conducted a playback experiment with marmoset monkeys and simulated “far-away” and “nearby” conspecifics using contact calls that differed in sound intensity. We found that marmoset monkeys increased the amplitude of their contact calls and produced such calls with shorter response latencies toward more distant conspecifics. The same was not true in response to changing levels of background noise. To account for how simulated conspecific distance can change both the amplitude and timing of vocal responses, we developed a model that incorporates dynamic interactions between the auditory system and limbic “drive” systems. Overall, our data show that, like humans, marmoset monkeys cooperatively control the acoustics of their vocalizations according to changes in listener distance, increasing the likelihood that a conspecific will hear their call. However, we propose that such cooperative vocal control is a system property that does not necessitate any particularly advanced sociocognitive skill. At least in marmosets, this vocal control can be parsimoniously explained by the regulation of arousal states across two interacting individuals via vocal feedback.

Download Full-text

Transcriptional Repression by Neuron-Restrictive Silencer Factor Is Mediated via the Sin3-Histone Deacetylase Complex

Molecular and Cellular Biology ◽

10.1128/mcb.20.6.2147-2157.2000 ◽

2000 ◽

Vol 20 (6) ◽

pp. 2147-2157 ◽

Cited By ~ 150

Author(s):

Avtar Roopra ◽

Lisa Sharling ◽

Ian C. Wood ◽

Teresa Briggs ◽

Ulla Bachfischer ◽

...

Keyword(s):

Histone Deacetylase ◽

Gene Transcription ◽

Transcriptional Repression ◽

Neuronal Cell ◽

Dominant Negative ◽

Specific Gene ◽

Aberrant Expression ◽

Neuronal Gene ◽

Repressor Element

ABSTRACT A large number of neuron-specific genes characterized to date are under the control of negative transcriptional regulation. Many promoter regions of neuron-specific genes possess the repressor element repressor element 1/neuron-restrictive silencing element (RE1/NRSE). Its cognate binding protein, REST/NRSF, is an essential transcription factor; its null mutations result in embryonic lethality, and its dominant negative mutants produce aberrant expression of neuron-specific genes. REST/NRSF acts as a regulator of neuron-specific gene expression in both nonneuronal tissue and developing neurons. Here, we shown that heterologous expression of REST/NRSF inSaccharomyces cerevisiae is able to repress transcription from yeast promoters engineered to contain RE1/NRSEs. Moreover, we have taken advantage of this observation to show that this repression requires both yeast Sin3p and Rpd3p and that REST/NRSF physically interacts with the product of the yeast SIN3 gene in vivo. Furthermore, we show that REST/NRSF binds mammalian SIN3A and HDAC-2 and requires histone deacetylase activity to repress neuronal gene transcription in both nonneuronal and neuronal cell lines. We show that REST/NRSF binding to RE1/NRSE is accompanied by a decrease in the acetylation of histones around RE1/NRSE and that this decrease requires the N-terminal Sin3p binding domain of REST/NRSF. Taken together, these data suggest that REST/NRSF represses neuronal gene transcription by recruiting the SIN3/HDAC complex.

Download Full-text

EFFECT OF HIRA PROTEIN ON TRANSCRIPTIONAL REGULATIONS OF GENES IN VERTEBRATE CELLS

Indonesian Journal of Chemistry ◽

10.22146/ijc.21605 ◽

2010 ◽

Vol 8 (3) ◽

pp. 454-458

Author(s):

Ahyar Ahmad

Keyword(s):

Genetic Analysis ◽

Transcriptional Repression ◽

Binding Ability ◽

Chromatin Dynamics ◽

Future Studies ◽

Lxxll Motif ◽

Major Break ◽

Related Proteins ◽

Chicken Dt40 Cell

For better understanding of DNA replicating-coupled chromatin assembly and transcription regulation in eukaryotes, we studied biochemical and genetic analysis of nuclear-related proteins from chicken DT40 cell lines. The genetic analysis of some nuclear proteins, such as HIRA and CAF-1, indicated that these proteins could play overlapping roles in chromatin dynamics and is consistent with the finding that HIRA protein exhibited binding ability to histones and ASF-1, as also ASF-1 bound directly with CAF-1p60. In this study, revealed not only that the N-terminal and C-terminal halves of HIRA mediate individually transcription repressions but also that even one of the seven WD dipeptide motifs and the LXXLL motif of HIRA are required for these mediations in vivo. Finally, we found that HIRA-mediated repression is sensitive to tricostatin TSA and it co-represses transcription together with HDAC-2. We believe our findings will contribute to a major break-through in future studies on the specific, individual roles of HIRA involved in numerous DNA-utilizing processes, through the formation and/or maintenance of the chromatin structure in vertebrate cells. Keywords: histone regulator, transcriptional repression, tricostatin, chromatin

Download Full-text

A Call to Expand Avian Vocal Development Research

Frontiers in Ecology and Evolution ◽

10.3389/fevo.2021.757972 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yen Yi Loo ◽

Kristal E. Cain

Keyword(s):

Life Histories ◽

Continuum Hypothesis ◽

Vocal Learning ◽

Neural Substrates ◽

Learning Ability ◽

Development Studies ◽

Vocal Development ◽

Vocal Production ◽

Development Patterns ◽

Vocal Control

Birds are our best models to understand vocal learning – a vocal production ability guided by auditory feedback, which includes human language. Among all vocal learners, songbirds have the most diverse life histories, and some aspects of their vocal learning ability are well-known, such as the neural substrates and vocal control centers, through vocal development studies. Currently, species are classified as either vocal learners or non-learners, and a key difference between the two is the development period, extended in learners, but short in non-learners. But this clear dichotomy has been challenged by the vocal learning continuum hypothesis. One way to address this challenge is to examine both learners and canonical non-learners and determine whether their vocal development is dichotomous or falls along a continuum. However, when we examined the existing empirical data we found that surprisingly few species have their vocal development periods documented. Furthermore, we identified multiple biases within previous vocal development studies in birds, including an extremely narrow focus on (1) a few model species, (2) oscines, (3) males, and (4) songs. Consequently, these biases may have led to an incomplete and possibly erroneous conclusions regarding the nature of the relationships between vocal development patterns and vocal learning ability. Diversifying vocal development studies to include a broader range of taxa is urgently needed to advance the field of vocal learning and examine how vocal development patterns might inform our understanding of vocal learning.

Download Full-text

Hearing and Neurodevelopmental Outcomes of Young Infants with Parechovirus-A and Enterovirus Meningitis: Cohort Study in Singapore Children and Literature Review

Journal of Pediatric Neurology ◽

10.1055/s-0040-1716366 ◽

2020 ◽

Author(s):

Elis Yuexian Lee ◽

Jessica Hui Yin Tan ◽

Chew Thye Choong ◽

Nancy Wen Sim Tee ◽

Chia Yin Chong ◽

...

Keyword(s):

Developmental Delay ◽

Oropharyngeal Dysphagia ◽

Significant Risk ◽

Developmental Outcomes ◽

Autism Spectrum ◽

Clinical Findings ◽

Cortical Blindness ◽

Speech Delay ◽

Neurodevelopmental Outcomes ◽

Young Infants

Abstract Parechovirus-A (PeV-A) and Enterovirus (EV) commonly cause childhood aseptic meningitis. Bacterial meningitis in children has been associated with devastating long-term sequelae. However, developmental outcomes are unclear in Parechovirus meningitis. This study aims to review the clinical findings and developmental outcomes of infants with PeV-A and EV meningitis. We performed a retrospective study of infants aged 90 days or younger being admitted to our hospital with PeV-A meningitis between November 2015 and July 2017, with positive cerebrospinal fluid (CSF) PeV-A PCR and negative blood and CSF bacterial cultures. Hearing and neurodevelopmental outcomes were compared with a previous cohort of infants aged 90 days or younger with EV meningitis admitted from January 2015 to December 2015. A total of 161 infants were included in our study, of which 68 infants (42.2%) had PeV-A meningitis and 93 infants (57.8%) had EV meningitis. We assessed their developmental outcome at 6 months, 1 year, and 2 years post-meningitis. At 2 years post-meningitis, three infants with PeV-A meningitis had developmental delay (5.5%), whereas none with EV meningitis had developmental delay. One patient had speech delay and autism spectrum disorder, while two had mild speech delay. When compared with our cohort of EV meningitis ≤90 days old, children with PeV-A meningitis ≤90 days old were more likely to have developmental delay 2 years post-meningitis (odds ratio 2.4, 95% confidence interval 2.0–3.0, p = 0.043). None of the patients with PeV-A or EV meningitis had sensorineural hearing loss or neurological sequelae, such as cortical blindness, oropharyngeal dysphagia, hydrocephalus, epilepsy, or cerebral palsy. Infants with PeV-A meningitis had a significant risk of developmental delay 2 years post-meningitis compared with those with EV meningitis. It is important to follow-up the developmental milestones of infants diagnosed with PeV-A meningitis for at least 2 years; and when they develop developmental delay, to ensure that they receive appropriate intervention.

Download Full-text