A5072548895- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Genetic Syndromes and Imprinting
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- Genomics and Chromatin Dynamics
- MicroRNA in disease regulation
- Ubiquitin and proteasome pathways
- Cancer-related molecular mechanisms research
- CRISPR and Genetic Engineering
- Retinal Development and Disorders
- RNA Research and Splicing
- Genomic variations and chromosomal abnormalities
- Cancer therapeutics and mechanisms
- Pluripotent Stem Cells Research
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Neuroendocrine regulation and behavior
- Macrophage Migration Inhibitory Factor
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Chromatin Remodeling and Cancer
- Nerve injury and regeneration
- Phosphodiesterase function and regulation
- Congenital heart defects research
- Mitochondrial Function and Pathology
National Taiwan University
2013-2024
Academia Sinica
2015-2016
National Taiwan University Hospital
2016
National Cheng Kung University
2015
University of North Carolina at Chapel Hill
2009-2014
University of Massachusetts Chan Medical School
2006-2010
Neuropsychiatric Research Institute
2006-2010
Alterations in GABAergic mRNA expression play a key role for prefrontal dysfunction schizophrenia and other neurodevelopmental disease. Here, we show that histone H3-lysine 4 methylation, chromatin mark associated with the transcriptional process, progressively increased at GAD1 gene promoters ( GAD2 , NPY SST ) human cortex (PFC) from prenatal to peripubertal ages throughout adulthood. included decreased H3K4-trimethylation, predominantly females conjunction risk haplotype 5′ end of ....
Expression of brain-derived neurotrophic factor (BDNF) is developmentally regulated in prefrontal cortex (PFC). The underlying molecular mechanisms, however, remain unclear. Here, we explore the role microRNAs (miRNAs) as post-transcriptional inhibitors BDNF. A sequential approach involving silico , miRNA microarray, situ hybridization and qRT–PCR studies identified a group 10 candidate miRNAs, segregating into five families (miR-30a-5p/b/c/d, miR-103/107, miR-191, miR-16/195, miR-495),...
Dysfunction of prefrontal cortex in schizophrenia includes changes GABAergic mRNAs, including decreased expression GAD1, encoding the 67 kDa glutamate decarboxylase (GAD67) GABA synthesis enzyme. The underlying molecular mechanisms remain unclear. Alterations DNA methylation as an epigenetic regulator gene are thought to play a role but this hypothesis is difficult test because no techniques available extract from GAD1 expressing neurons efficiently human postmortem brain. Here, we present...
Abstract Background DNA-protein interactions in mature brain are increasingly recognized as key regulators for behavioral plasticity and neuronal dysfunction chronic neuropsychiatric disease. However, chromatin assays typically lack single cell resolution, therefore little is known about regulation of differentiated nuclei that reside parenchyma intermingled with various types non-neuronal cells. Results Here, we describe a protocol to selectively tag from adult – either by (anti-NeuN)...
Abstract RBFOX3 mutations are linked to epilepsy and cognitive impairments, but the underlying pathophysiology of these disorders is poorly understood. Here we report replication human symptoms in a mouse model with disrupted Rbfox3 . knockout mice displayed increased seizure susceptibility decreased anxiety-related behaviors. Focusing on hippocampal phenotypes, found showed expression plasticity genes Egr4 Arc synaptic transmission were defective mutant perforant pathway. The dentate...
Dysfunction of RBFOX3 has been identified in neurodevelopmental disorders such as autism spectrum disorder, cognitive impairments and epilepsy a causal relationship with these diseases previously demonstrated Rbfox3 homozygous knockout mice. Despite the importance during neurodevelopment, function regarding neurogenesis synaptogenesis remains unclear. To address this critical question, we profiled developmental expression pattern brain wild-type mice analyzed volume, disease-relevant...
RTL1/PEG11, which has been associated with anxiety disorders, is a retrotransposon-derived imprinted gene in the placenta. However, imprinting patterns and functions of RTL1 brain have not well-investigated. We found Rtl1 was paternally, but maternally, expressed stem, thalamus, hypothalamus mice, status maintained human brain. Paternal knockout (Rtl1m+/p-) mice had higher neonatal death rates due to impaired suckling, low body weights beginning on embryonic day 16.5. High paternal...
Genomic imprinting describes an epigenetic process through which genes can be expressed in a parent-of-origin-specific manner. The monoallelic expression of imprinted renders them particularly susceptible to disease causing mutations. A large proportion are the brain, but little is known about their functions. Indeed, it has proven difficult identify cell type-specific due heterogeneity types within brain. Here we used laser capture microdissection visual cortical neurons and found evidence...
RBFOX3/NeuN is a neuronal splicing regulator involved in neural circuitry balance, as well neurogenesis and synaptogenesis. Rbfox3 expressed neurons; however, the retina, expression restricted to cells ganglion cell layer some of inner nuclear layer. layer-specific manner which implies functional role, role RBFOX3 retina unknown. homozygous knockout (Rbfox3-/-) mice exhibit deficits visual learning; therefore, understanding critical for interpreting behavioral results. We found was...
The central amygdala (CeA) nucleus, a subcortical structure composed of mostly GABA-releasing (GABAergic) neurons, controls fear expression via projections to downstream targets in the hypothalamus and brainstem. CeA consists lateral (CeL) medial (CeM) subdivisions. CeL strongly gates information transfer CeM, main output station amygdala, but little is known about functional organization local circuits this region. Using cluster analysis, we identified two major electrophysiologically...
Epilepsy is a common neurological disorder, which has been linked to mutations or deletions of RNA binding protein, fox-1 homolog ( Caenorhabditis elegans ) 3 RBFOX3 )/ NeuN , neuronal splicing regulator. However, the mechanism seizure mediation by remains unknown. Here, we show that mice with deletion Rbfox3 in gamma-aminobutyric acid (GABA) ergic neurons exhibit spontaneous seizures and high premature mortality due increased presynaptic release, postsynaptic potential, excitability,...
Abstract Genomic imprinting predominantly occurs in the placenta and brain. Few imprinted microRNAs have been identified brain, their functional roles brain are not clear. Here we show paternal, but maternal, expression of MIR125B2 human mouse Moreover, Mir125b-2 m − /p mice showed impaired learning memory, anxiety, whose functions were hippocampus-dependent. Hippocampal granule cells from displayed increased neuronal excitability, excitatory synaptic transmission, decreased inhibitory...
Visual system development is light-experience dependent, which strongly implicates epigenetic mechanisms in light-regulated maturation. Among many processes, genomic imprinting an mechanism through monoallelic gene expression occurs a parent-of-origin-specific manner. It unknown if contributes to visual development. We profiled the transcriptome and imprintome during critical periods of mouse under normal- dark-rearing conditions using B6/CAST F1 hybrid mice. identified experience-regulated,...
Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder, and the exact causal mechanism unknown. Dysregulated allele-specific expression (ASE) has been identified in persons with ASD; however, comprehensive analysis of ASE not conducted family quartet ASD. To fill this gap, we analyzed using genomic DNA from parent offspring RNA offspring's postmortem prefrontal cortex (PFC); one two had diagnosed DNA- RNA-sequencing revealed distinct patterns PFC both offspring....
Hybrid species have more genetic diversity than their parents. However, the impact of hybrid genome reciprocal crosses on brain function remains largely unknown. We performed behavioral, molecular, and neuronal analyses C57BL/6J mice (B6), CAST/EiJ (CAST), resulting from two strains, B6/CAST F1i F1r, respectively. displayed greater motor strength coordination, food grinding, social dominance, less sociability compared to parental strains. Parental origin influenced body weight, locomotor...
Genomic imprinting is an epigenetic mechanism causing monoallelic expression in a parent-of-origin-specific manner. Disruption of imprinted genes causes various neurological and psychiatric disorders. However, the role brain largely unknown. Different cell types within distinct regions can influence genomic status, but single have not been characterized on genome-wide scale. To address this critical question, we used multi-stage approach, which combined genetically engineered mice with...