A5040345507- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- MicroRNA in disease regulation
- Axon Guidance and Neuronal Signaling
- Neuroscience and Neuropharmacology Research
- Congenital heart defects research
- Advanced Electron Microscopy Techniques and Applications
- Cancer-related molecular mechanisms research
- Cellular transport and secretion
- Genomics and Chromatin Dynamics
- Glioma Diagnosis and Treatment
- Birth, Development, and Health
- Caveolin-1 and cellular processes
- Single-cell and spatial transcriptomics
- Plant Reproductive Biology
- Cell Adhesion Molecules Research
- Advanced biosensing and bioanalysis techniques
- Pluripotent Stem Cells Research
- Fetal and Pediatric Neurological Disorders
- Ion channel regulation and function
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
Rutgers, The State University of New Jersey
2014-2023
Johnson University
2013-2023
Yale University
2005-2009
University of Zagreb
2002-2003
Tourette's syndrome (TS) is a genetically influenced developmental neuropsychiatric disorder characterized by chronic vocal and motor tics. We studied Slit Trk-like 1 (SLITRK1) as candidate gene on chromosome 13q31.1 because of its proximity to de novo chromosomal inversion in child with TS. Among 174 unrelated probands, we identified frameshift mutation two independent occurrences the identical variant binding site for microRNA hsa-miR-189. These variants were absent from 3600 control...
The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that centrally involved in cognition. We assessed more than 600,000 single-nucleus transcriptomes from adult human, chimpanzee, macaque, and marmoset dlPFC. Although most cell subtypes defined transcriptomically are conserved, we detected several exist only a subset species as well substantial species-specific molecular differences across homologous neuronal, glial, non-neural subtypes. latter...
The disappearance of fine motor control Manual skills are much better developed in primates than rodents. This difference is part due to species-specific differences the motoneurons by brain. Gu et al. used a range approaches evaluate potential corticospinal tract projections neonatal mice. These exist immediately after birth but disappear within first 2 postnatal weeks owing actions plexin A, member semaphorin receptor family. Targeted deletion receptors mutant mice prevented elimination...
Cortical excitatory glutamatergic projection neurons and inhibitory GABAergic interneurons follow substantially different developmental programs. In rodents, originate from progenitors within the dorsal forebrain, whereas arise in ventral forebrain. contrast, it has been proposed that humans, majority of cortical suggesting their origin migration is complex evolutionarily divergent. However, whether molecularly defined human interneuron subtypes distinct progenitors, including those remains...
Significance The neocortex is an intricate and diverse cellular network in the brain, generating complex thought voluntary motor behavior. Although recent attention has focused on genome transcriptome, our goal to study role of posttranscriptional processing mRNA translation neocortical development. In this work, we show that protein components actively translating ribosomes their cargo developing depend temporally specific action RNA-binding protein, Hu antigen R (HuR). We further HuR...
Abstract Abnormalities in neocortical and synaptic development are linked to neurodevelopmental disorders. However, the molecular cellular mechanisms governing initial synapse formation prenatal neocortex remain poorly understood. Using polysome profiling coupled with snRNAseq on human cortical samples at various fetal phases, we identify mRNAs, including those encoding proteins, finely controlled translation distinct cell populations of developing frontal neocortices. Examination murine...
Abstract Tourette syndrome (TS) is an inherited developmental neuropsychiatric disorder characterized by vocal and motor tics. Multiple lines of neurophysiological evidence implicate dysfunction in the corticostriatal‐thalamocortical circuits etiology TS. We recently identified rare sequence variants Slit Trk‐like family member 1 ( SLITRK1 ) gene associated with SLITRK1, a single‐pass transmembrane protein, displays similarities to SLIT secreted ligands, which have roles axonal repulsion...
Protein synthesis must be finely tuned in the developing nervous system as final essential step of gene expression. This study investigates architecture ribosomes from neocortex during neurogenesis, revealing Ebp1 a high-occupancy 60S peptide tunnel exit (TE) factor protein at near-atomic resolution by cryoelectron microscopy (cryo-EM). Ribosome profiling demonstrated Ebp1-60S binding is highest start codon initiation and N-terminal elongation, regulating ribosome occupancy these codons....
BackgroundMutations in the X-linked gene DDX3X account for approximately 2% of intellectual disability females, often comorbid with behavioral problems, motor deficits, and brain malformations. encodes an RNA helicase emerging functions corticogenesis synaptogenesis.MethodsWe generated a Ddx3x haploinsufficient mouse (Ddx3x+/− females) construct validity loss-of-function mutations. We used standardized batteries to assess developmental milestones adult behaviors, as well magnetic resonance...
Neocortical development requires tightly controlled spatiotemporal gene expression. However, the mechanisms regulating ribosomal complexes and timed specificity of neocortical mRNA translation are poorly understood. We show that active (polysomes) contain protein subsets undergo dynamic rearrangements during mouse development. Ribosomal within polysome is regulated by arrival in-growing thalamic axons, which secrete morphogen Wingless-related MMTV (mouse mammary tumor virus) integration site...
Early regional patterning and laminar position of cortical projection neurons is determined by activation deactivation transcriptional factors (TFs) RNA binding proteins (RBPs) that regulate spatiotemporal framework neurogenetic processes (proliferation, migration, aggregation, postmigratory differentiation, molecular identity acquisition, axonal growth, dendritic development, synaptogenesis) within transient cellular compartments. Deep-layer (DPN), subplate (SPN), Cajal–Retzius (CRN) are...
Abstract Potassium (K + ) channels are robustly expressed during prenatal brain development, including in progenitor cells and migrating neurons, but their function is poorly understood. Here, we investigate the role of voltage-gated K channel KCNB1 (Kv2.1) neocortical development. Neuronal migration glutamatergic neurons was impaired neocortices null mice. Migratory defects persisted into adult brains, along with disrupted morphology synaptic connectivity. Mice developed seizure phenotype,...
Abstract PIWI-interacting RNAs (piRNAs) and their associated PIWI proteins play an important role in repressing transposable elements animal germlines. However, little is known about the function of piRNAs developing brain. Here, we investigated family member, Piwi-like protein 1 (Piwil1; also as Miwi mouse) mouse neocortex. Using a Piwil1 knock-out ( KO) strain, found that essential for several steps neocorticogenesis, including neocortical cell cycle, neuron migration dendritogenesis....
Background/Objectives: Previous developmental studies pointed out the complexity of morphogenetic events in interhemispheric cerebral wall during formation corpus callosum. However, changes morphology individual cells region developing dorsal allocortex have not been studied. The aim this study was to analyze and maturational different cell classes subcallosal zone human fetal brain (22 28 weeks post ovulation), using Golgi acetylcholinesterase staining. Results: occupies a paramedian...
Abstract Homozygous mutations in the gene encoding scavenger mRNA-decapping enzyme, DcpS, have been shown to underlie developmental delay and intellectual disability. Intellectual disability is associated with both abnormal neocortical development mRNA metabolism. However, role of DcpS its decapping activity neuronal unknown. Here, we show that human neurons derived from patients a mutation compromised differentiation neurite outgrowth. Moreover, developing mouse neocortex, required for...
Extrinsic molecules such as morphogens can regulate timed mRNA translation events in developing neurons. In particular, Wingless-type MMTV integration site family, member 3 (Wnt3), was shown to the of Foxp2 encoding a Forkhead transcription factor P2 neocortex. However, Wnt receptor that possibly mediates these remains unknown. Here, we report Frizzled 7 (Fzd7) Wnt3 lays downstream Wnt3-regulated translation. Fzd7 proteins co-localize with ligands neocortices. addition, overlap...
SUMMARY Protein synthesis must be finely tuned in the nervous system, as it represents an essential feature of neurodevelopmental gene expression, and dominant pathology neurological disease. However, architecture ribosomal complexes developing mammalian brain has not been analyzed at high resolution. This study investigates ribosomes ex vivo from embryonic perinatal mouse neocortex, revealing Ebp1 a 60S peptide tunnel exit binding factor near-atomic resolution by multiparticle cryo-electron...
ABSTRACT Background Mutations in the X-linked gene DDX3X account for ~2% of intellectual disability females, often co-morbid with behavioral problems, motor deficits, and brain malformations. encodes an RNA helicase emerging functions corticogenesis synaptogenesis. Methods We generated a Ddx3x haploinsufficient mouse ( +/− ) construct validity loss-of-function mutations. used standardized batteries to assess developmental milestones adult behaviors, as well magnetic resonance imaging...