Kenneth Y. Kwan
A5007105466- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- Neuroscience and Neuropharmacology Research
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Congenital heart defects research
- Axon Guidance and Neuronal Signaling
- Autism Spectrum Disorder Research
- Cancer Genomics and Diagnostics
- Cellular Mechanics and Interactions
- MicroRNA in disease regulation
- Fetal and Pediatric Neurological Disorders
- Down syndrome and intellectual disability research
- CRISPR and Genetic Engineering
- Developmental Biology and Gene Regulation
- RNA modifications and cancer
- Neural dynamics and brain function
- Cell Image Analysis Techniques
- Tactile and Sensory Interactions
- Single-cell and spatial transcriptomics
- Analog and Mixed-Signal Circuit Design
University of Michigan
2014-2025
Michigan United
2023
Neuroscience Institute
2018-2020
Institute of Human Genetics
2018
Rutgers, The State University of New Jersey
2017
Yale University
2005-2016
University of Kentucky
2005
Robarts Clinical Trials
2000
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...
Zoltán Molnár1 and Kenneth Y. Kwan2 1Department of Physiology, Anatomy Genetics, Sherrington Building, University Oxford, Oxford OX1 3PT, United Kingdom 2Michigan Neuroscience Institute (MNI), Department Human Michigan, Ann Arbor, Michigan 48109, USA Correspondence: zoltan.molnar{at}dpag.ox.ac.uk; kykwan{at}umich.edu
Neocortical projection neurons exhibit layer-specific molecular profiles and axonal connections. Here we show that the identities of early-born subplate deep-layer are not acquired solely during generation or shortly thereafter but undergo progressive postmitotic refinement mediated by SOX5. Fezf2 Bcl11b, transiently expressed in all subtypes newly postmigratory neurons, subsequently downregulated layer 6 thereby establishing their 5-enriched postnatal patterns. In Sox5-null mice, this...
Pyramidal neurons of the cerebral cortex display marked layer- and subtype-specific differences in their axonal projections dendritic morphologies. Here we show that transcription factor Zfp312 is selectively expressed by layer V VI subcortical projection pyramidal progenitor cells. Knocking down with small interfering RNAs dramatically reduced number from deep-layer altered morphology. In contrast, misexpression cortically projecting layers II III induced expression Tbr1, a enriched...
The corticospinal (CS) tract is involved in controlling discrete voluntary skilled movements mammals. CS arises exclusively from layer (L) 5 projection neurons of the cerebral cortex, and its formation requires L5 activity Fezf2 (Fezl, Zfp312). How this L5-specific pattern expression axonal connectivity established with such remarkable fidelity had remained elusive. Here we show that transcription factor TBR1 directly binds locus represses L6 corticothalamic to restrict origin L5. In Tbr1...
Mutations in a number of chromatin modifiers are associated with human neurological disorders. KDM5C, histone H3 lysine 4 di- and tri-methyl (H3K4me2/3)-specific demethylase, is frequently mutated X-linked intellectual disability (XLID) patients. Here, we report that disruption the mouse Kdm5c gene recapitulates adaptive cognitive abnormalities observed XLID, including impaired social behavior, memory deficits, aggression. Kdm5c-knockout brains exhibit abnormal dendritic arborization, spine...
Abstract Long Interspersed Element-1 (LINE-1) retrotransposition contributes to inter- and intra-individual genetic variation occasionally can lead human disorders. Various strategies have been developed identify human-specific LINE-1 (L1Hs) insertions from short-read whole genome sequencing (WGS) data; however, they limitations in detecting complex repetitive genomic regions. Here, we a computational tool (PALMER) used it 203 non-reference L1Hs the NA12878 benchmark genome. Using PacBio...
There is growing interest to investigate classic psychedelics as potential therapeutics for mental illnesses. Previous studies have demonstrated that one dose of psilocybin leads persisting neural and behavioral changes. The durability psilocybin's effects suggests there are likely alterations gene expression at the transcriptional level. In this study, we performed single-nucleus RNA sequencing dorsal medial frontal cortex male female mice. Samples were collected 1, 2, 4, 24, or 72 hours...
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...
Local mRNA translation in growing axons allows for rapid and precise regulation of protein expression response to extrinsic stimuli. However, the role local mature CNS is unknown. Such a mechanism requires presence translational machinery associated mRNAs circuit-integrated brain axons. Here we use combination genetic, quantitative imaging super-resolution microscopy approaches show that mammalian contain ribosomes, regulator FMRP subset targets. This axonal with Fragile X granules (FXGs),...
Abstract The brain is a genomic mosaic shaped by cellular responses to genome damage. Here, we manipulate somatic stability conditional Knl1 deletion from embryonic mouse brain. KNL1 mutations cause microcephaly and mediates the spindle assembly checkpoint, safeguard against chromosome missegregation aneuploidy. We find that following deletion, segregation errors in mitotic neural progenitor cells give rise DNA damage on missegregated chromosomes. This triggers rapid p53 activation robust...
Down syndrome (DS) is caused by the trisomy of human chromosome 21 (HSA21). A major challenge in DS research to identify HSA21 genes that cause specific symptoms. cell adhesion molecule (DSCAM) encoded a gene. Previous studies have shown protein level Drosophila homolog DSCAM determines size presynaptic terminals. However, whether triplication contributes development remains unknown. Here, we show levels regulate GABAergic synapses formed on neocortical pyramidal neurons (PyNs). In Ts65Dn...
Abstract When somatic cells acquire complex karyotypes, they often are removed by the immune system. Mutant that evade surveillance can lead to cancer. Neurons with karyotypes arise during neurotypical brain development, but neurons almost never origin of cancers. Instead, mutations in bring about neurodevelopmental disorders, and contribute polygenic landscape neuropsychiatric neurodegenerative disease. A subset human harbors idiosyncratic copy number variants (CNVs, “CNV neurons”),...