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Major histocompatibility complex class I (MHCI) genes were discovered unexpectedly in healthy CNS neurons in a screen for genes regulated by neural activity. In mice lacking just 2 of the 50+ MHCI genes H2-K(b) and H2-D(b), ocular dominance (OD) plasticity is enhanced. Mice lacking PirB, an MHCI receptor, have a similar phenotype. H2-K(b) and H2-D(b) are(More)
There are more than 50 class I MHC (MHCI) molecules in the mouse genome, some of which are now known to be expressed in neurons; however, the role of classical MHCI molecules in synaptic plasticity is unknown. We report that the classical MHCI molecules, H2-K(b) and H2-D(b), are co-expressed by Purkinje cells (PCs). In the cerebellum of mice deficient for(More)
The mouse brain contains genetically distinct cells that differ with respect to chromosome number manifested as aneuploidy (Rehen et al., 2001); however, the relevance to humans is not known. Here, using double-label fluorescence in situ hybridization for the autosome chromosome 21 (chromosome 21 point probes combined with chromosome 21 "paint" probes),(More)
We used single-cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and postmortem human brains. We identified aneuploid neurons, as well as numerous subchromosomal CNVs in euploid neurons. Neurotypic hiPSC-derived neurons had larger CNVs than fibroblasts, and several large(More)
The existence of aneuploid cells within the mammalian brain has suggested the influence of genetic mosaicism on normal neural circuitry. However, aneuploid cells might instead be glia, nonneural, or dying cells, which are irrelevant to direct neuronal signaling. Combining retrograde labeling with FISH for chromosome-specific loci, distantly labeled(More)
Recent studies based predominantly on nucleotide hybridization techniques have identified aneuploid neurons and glia in the normal brain. To substantiate these findings and address how neural aneuploidy arises, we examined individual neural progenitor cells (NPCs) undergoing mitosis. Here we report the identification of chromosomal segregation defects in(More)
Frequent chromosomal aneuploidy has recently been discovered in normal neurons of the developing and mature murine CNS. Toward a more detailed understanding of aneuploidy and its effects on normal CNS cells, we examined the genomes of cells in the postnatal subventricular zone (SVZ), an area that harbors a large number of neural stem and progenitor cells(More)
DNA methylation-mediated epigenetic regulation plays critical roles in regulating mammalian gene expression, but its role in normal brain function is not clear. Methyl-CpG binding protein 1 (MBD1), a member of the methylated DNA-binding protein family, has been shown to bind methylated gene promoters and facilitate transcriptional repression in vitro. Here(More)
LINE-1 (L1) elements are retrotransposons that insert extra copies of themselves throughout the genome using a 'copy and paste' mechanism. L1s comprise nearly approximately 20% of the human genome and are able to influence chromosome integrity and gene expression upon reinsertion. Recent studies show that L1 elements are active and 'jumping' during neuronal(More)
Aneuploid neurons populate the normal adult brain, but the cause and the consequence of chromosome abnormalities in the CNS are poorly defined. In the adult cerebral cortex of three genetic mutants, one of which is a mouse model of the human neurodegenerative disease ataxia-telangiectasia (A-T), we observed divergent levels of sex chromosome (XY)(More)