A5101622125- RNA Research and Splicing
- Neuroendocrine regulation and behavior
- Genetics, Aging, and Longevity in Model Organisms
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- Circadian rhythm and melatonin
- Autism Spectrum Disorder Research
- Infant Health and Development
- Congenital heart defects research
- RNA regulation and disease
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Animal Vocal Communication and Behavior
- Neurobiology and Insect Physiology Research
- Child and Adolescent Psychosocial and Emotional Development
- Neuroscience and Neuropharmacology Research
- Virus-based gene therapy research
- Identification and Quantification in Food
- CRISPR and Genetic Engineering
- interferon and immune responses
- Herpesvirus Infections and Treatments
- Cellular transport and secretion
- Lepidoptera: Biology and Taxonomy
- Genetic diversity and population structure
- Chromatin Remodeling and Cancer
Salk Institute for Biological Studies
2023-2024
Washington University in St. Louis
2013-2023
University of Missouri–St. Louis
2021
Center for Neurosciences
2018
Yale University
2018
University of British Columbia
2018
University of California, San Francisco
2018
Hussman Institute for Autism
2018
University of California, Los Angeles
2018
Universidad de Salamanca
2018
Pattern formation in the brain Neurons developing cooperate to build circuits. Mountoufaris et al. found that ∼50 variable protocadherin genes support a combinatorial identity code allows millions of olfactory neuron axons sort into ∼2000 glomeruli. Sharing receptors drives one glomerulus, and diversity multiple touch each other as they converge. On hand, Chen single C-type underlies tiled distribution serotonergic neurons throughout central nervous system. These neurons, which share...
Mutations in the transcription factor Forkhead box p1 ( FOXP1 ) are causative for neurodevelopmental disorders such as autism. However, function of within brain remains largely uncharacterized. Here, we identify gene expression program regulated by FoxP1 both human neural cells and patient-relevant heterozygous Foxp1 mouse brains. We demonstrate a role transcriptional regulation autism-related pathways well genes involved neuronal activity. show that regulates excitability striatal medium...
The immense molecular diversity of neurons challenges our ability to understand the genetic and cellular etiology neuropsychiatric disorders. Leveraging knowledge from neurobiology may help parse complexity: identifying genes important for a circuit that mediates particular symptom disease identify polymorphisms contribute risk as whole. serotonergic system has long been suspected in disorders have symptoms repetitive behaviors resistance change, including autism. We generated bacTRAP mouse...
Prey respond to predators by altering their behavior optimize own fitness and survival. Specifically, prey are known avoid predator-occupied territories reduce risk of harm or injury themselves progeny. We probe the interactions between Caenorhabditis elegans its naturally cohabiting predator Pristionchus uniformis reveal pathways driving changes in behavior. While C. prefers lay eggs on a bacteria food lawn, presence inside lawn induces more away from that lawn. confirm this change egg...
Neurofibromatosis type 1 (NF1) is a monogenic neurodevelopmental disease caused by germline loss‐of‐function mutations in the NF1 tumor suppressor gene. Cognitive impairments are observed approximately 80% of children with this disease, 45–60% exhibiting autism spectrum disorder (ASD) symptomatology. In light high comorbidity rate between ASD and NF1, we assessed early communicative behavior maternal‐separation induced pup ultrasonic vocalizations (USV) developmental milestones two distinct...
Abstract Quaking RNA binding protein (QKI) is essential for oligodendrocyte development as myelination requires myelin basic mRNA regulation and localization by the cytoplasmic isoforms (e.g., QKI-6). QKI-6 also highly expressed in astrocytes, which were recently demonstrated to have regulated localization. Here, we define targets of QKI mouse brain via CLIPseq show that binds 3′UTRs a subset astrocytic mRNAs. Binding enriched near stop codons, mediated partially QKI-binding motifs (QBMs),...
Abstract The function of regulatory elements is highly dependent on the cellular context, and thus for understanding associated with psychiatric diseases these would ideally be studied in neurons a living brain. Massively Parallel Reporter Assays (MPRAs) are molecular genetic tools that enable functional screening hundreds predefined sequences single experiment. These assays have not yet been adapted to query specific cell types vivo complex tissue like mouse Here, using test-case 3′UTR MPRA...
Mice produce ultrasonic vocalizations (USV) in multiple communicative contexts, including adult social interaction (e.g., male to female courtship), as well pup calls when separated from the dam. Assessment of USV has been widely applied models and disorders, dozens which have shown alterations this conserved behavior. However, features such call production rate can vary substantially even within experimental groups it is unclear what extent aspects represent stable trait-like influences or...
Genetic disruptions of the forkhead box transcription factor FOXP2 in humans cause an autosomal-dominant speech and language disorder. While expression pattern are highly conserved, its role specific brain areas for mammalian social behaviors remains largely unknown. Here we studied mice carrying a homozygous cortical Foxp2 deletion. The postnatal development gross morphological architecture mutant was indistinguishable from wildtype (WT) littermates. Unbiased behavioral profiling adult...
Serotonergic dysregulation is implicated in numerous psychiatric disorders. Serotonin plays widespread trophic roles during neurodevelopment; thus perturbations to this system development may increase risk for neurodevelopmental Epidemiological studies have examined association between selective serotonin reuptake inhibitor (SSRI) treatment pregnancy and increased autism spectrum disorder (ASD) offspring. It unclear from these whether ASD susceptibility purely related maternal diagnosis, or...
Identifying neurons essential for the generation of breathing and related behaviors such as vocalisation is an important question human health. The targeted loss preBötzinger Complex (preBötC) glutamatergic neurons, including those that express high levels somatostatin protein (SST neurons), eliminates normal in adult rats. Whether preBötC SST represent a functionally specialised population unknown. We tested effects on respiratory vocal eliminating neuron glutamate release by...
Mice produce ultrasonic vocalizations (USVs) in a variety of social situations, and USVs have been leveraged to study many neurological diseases including verbal dyspraxia, depression, autism stuttering. Pups isolation calls, common USV, spontaneously when they are isolated from their mother during the first 2 weeks life. Several genetic manipulations affect (and often reduce) pup calls mice. To facilitate use this assay as means testing whether significant functional differences genotypes...
CELF6 is a CELF-RNA-binding protein, and thus part of protein family with roles in human disease; however, its mRNA targets the brain are largely unknown. Using cross-linking immunoprecipitation sequencing (CLIP-seq), we define CNS targets, which enriched for 3′ UTRs synaptic protein-coding genes. massively parallel reporter assay framework, test consequence expression on target sequences, without mutating putative binding motifs. Where exerts an effect it to decrease RNA abundance, reversed...
Abstract In addition to gene expression differences in distinct cell types, there is substantial post‐transcriptional regulation driven part by RNA binding proteins (RBPs). Loss‐of‐function RBP mutations have been associated with neurodevelopmental disorders, such as Fragile‐X syndrome and syndromic autism. Work performed animal models elucidate the influence of disorder‐associated RBPs on behaviors has showed a connection between normal conditioned learning. We previously reported cognitive...
Abstract This article documents the addition of 92 microsatellite marker loci to Molecular Ecology Resources Database. Loci were developed for following species: Anopheles minimus , An. sinensis, dirus, Calephelis mutica, Lutjanus kasmira, Murella muralis and Orchestia montagui . These cross‐tested on arizonensi, borealis, nemesis, virginiensis bengalensis.
Abstract The function of regulatory elements is highly dependent on the cellular context, and thus for understanding associated with psychiatric diseases these would ideally be studied in neurons a living brain. Massively Parallel Reporter Assays (MPRAs) are molecular genetic tools that enable functional screening hundreds predefined sequences single experiment. These assays have not yet been adapted to query specific cell types vivo complex tissue like mouse Here, using test-case 3′UTR MPRA...
Abstract CELF6 is a RNA-binding protein in family of proteins with roles human health and disease, however little known about the mRNA targets or vivo function this protein. We utilized CLIP-Seq to identify, for first time, identify hundreds transcripts bound by brain. found these are disproportionately mRNAs coding synaptic proteins. then conducted functional validation targets, testing greater than 400 sequence elements their activity, applying massively parallel reporter assay framework...
Abstract Neurexins and their canonical binding partners, neuroligins, are localized to neuronal pre-, post-synapses, respectively, but less is known about role in driving behaviors. Here, we use the nematode C. elegans show that neurexin, not neuroligin, required for avoiding specific chemorepellents. We find adults with knockouts of entire neurexin locus exhibit a strong avoidance deficit response glycerol weaker defect copper. Notably, ( nrx-1 ) locus, like its mammalian homologs, encodes...
Abstract Neurexins and their canonical binding partners, neuroligins, are localized to neuronal pre-, post-synapses, respectively, but less is known about role in driving behaviors. Here, we use the nematode C. elegans show that neurexin, not neuroligin, required for avoiding specific chemorepellents. We find adults with knockouts of entire neurexin locus exhibit a strong avoidance deficit response glycerol weaker defect copper. Notably, (nrx-1) locus, like its mammalian homologs, encodes...
Summary Serotonergic dysregulation is implicated in psychiatric disorders, including autism spectrum disorders (ASD). Epidemiological studies suggest selective serotonin reuptake inhibitor (SSRI) treatment during pregnancy may increase ASD risk offspring, however it unclear from these whether susceptibility related to the maternal diagnosis or if poses additional risk. Here, we exposed mouse dams fluoxetine and characterized offspring isolate possible effects of SSRI exposure on ASD-relevant...
Abstract Quaking RNA binding protein(QKI) is essential for oligodendrocyte development as myelination requires MBP mRNA regulation and localization by the cytoplasmic isoforms(e.g. QKI-6). QKI-6 also highly expressed in astrocytes, which were recently demonstrated to have regulated localization. Here, we show via CLIPseq that binds 3’ UTRs of a subset astrocytic mRNAs, including many enriched peripheral processes. Binding near stop codons, mediated partially QKI motifs(QBMs) yet spreads...
ABSTRACT Methamphetamine addiction remains a major public health concern in the United States that has paralleled opioid epidemic. Psychostimulant use disorders have heritable genetic component unexplained. targets membrane and vesicular transporters to increase synaptic dopamine, norepinephrine, serotonin. We previously identified Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) as quantitative trait gene underlying methamphetamine behavioral sensitivity. encodes RNA-binding protein...