A5017540861- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Single-cell and spatial transcriptomics
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Axon Guidance and Neuronal Signaling
- Congenital heart defects research
- Epigenetics and DNA Methylation
- Neonatal and fetal brain pathology
- Fetal and Pediatric Neurological Disorders
- MicroRNA in disease regulation
- Wnt/β-catenin signaling in development and cancer
- Epilepsy research and treatment
- Glioma Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Kruppel-like factors research
- Pluripotent Stem Cells Research
- Zebrafish Biomedical Research Applications
- Autoimmune Neurological Disorders and Treatments
- Renal and related cancers
- Tuberous Sclerosis Complex Research
- Genetics, Aging, and Longevity in Model Organisms
- Immune cells in cancer
- RNA modifications and cancer
University of California, San Francisco
2016-2025
Broad Center
2016-2025
Austrian Cluster for Tissue Regeneration
2024
University of California, Los Angeles
2024
University of San Francisco
2022-2024
Denali Therapeutics (United States)
2024
Neurological Surgery
2002-2024
Broad Institute
2016-2022
Universitat de Barcelona
2015
Medical University of Vienna
2015
Building the human brain As develops, neurons migrate from zones of proliferation to their final locations, where they begin build circuits. Paredes et al. have discovered that shortly after birth, a group proliferates near ventricles migrates in chains alongside circulatory vessels into frontal lobes (see Perspective by McKenzie and Fishell). Young postnatally anterior cingulate cortex then develop features inhibitory interneurons. The number migratory cells decreases over first 7 months...
We report the clinical features, comorbidities, and outcome of 22 newly identified patients with antibodies to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR).This was a retrospective review diagnosed between May 2009 March 2014. Immunologic techniques have been reported previously.Patients' median age 62 years (range 23-81; 14 female). Four syndromes were identified: 12 (55%) presented distinctive limbic encephalitis (LE), 8 (36%) dysfunction along multifocal/diffuse...
Evolutionary development of the human brain is characterized by expansion various regions. Here, we show that developmental processes specific to humans are responsible for malformations cortical (MCDs), which result in delay and epilepsy children. We generated a cerebral organoid model tuberous sclerosis complex (TSC) identified neural stem cell type, caudal late interneuron progenitor (CLIP) cells. In TSC, CLIP cells over-proliferate, generating excessive interneurons, tumors,...
Abstract Neuroanatomists have long speculated that expanded primate brains contain an increased morphological diversity of inhibitory neurons (INs) 1 , and recent studies identified primate-specific neuronal populations at the molecular level 2 . However, we know little about developmental mechanisms specify evolutionarily novel cell types in brain. Here, reconstruct gene expression trajectories specifying INs generated throughout neurogenic period macaques mice by analysing transcriptomes...
Interactions between angiogenesis and neurogenesis regulate embryonic brain development. However, a comprehensive understanding of the stages vascular cell maturation is lacking, especially in prenatal human brain. Using fluorescence-activated sorting, single-cell transcriptomics, histological ultrastructural analyses, we show that an ensemble endothelial mural subtypes tile vasculature during second trimester. These cells follow distinct developmental trajectories utilize diverse signaling...
We analyzed >700,000 single-nucleus RNA sequencing profiles from 106 donors during prenatal and postnatal developmental stages identified lineage-specific programs that underlie the development of specific subtypes excitatory cortical neurons, interneurons, glial cell types, brain vasculature. By leveraging chromatin accessibility data, we delineated enhancer gene regulatory networks transcription factors control commitment lineages. intersecting our results with genetic risk for human...
The development of the human neocortex is highly dynamic, involving complex cellular trajectories controlled by gene regulation1. Here we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 neocortical samples encompassing both prefrontal cortex primary visual cortex. These span five main developmental stages, ranging first trimester to adolescence. In parallel, performed spatial transcriptomic analysis on a subset illustrate organization intercellular...
Focal cortical dysplasia (FCD) is a common and important cause of medically intractable epilepsy. In patients with temporal lobe epilepsy in several animal models, compromised neuronal inhibition, mediated by GABA, contributes to seizure genesis. Although reduction GABAergic interneuron density has been reported FCD tissue samples, there little available information on the resulting physiological changes synaptic inhibition potential contribution these epileptogenesis dysplastic human brain....
The human amygdala grows during childhood, and its abnormal development is linked to mood disorders. primate contains a large population of immature neurons in the paralaminar nuclei (PL), suggesting protracted possibly neurogenesis. Here we studied PL from embryonic stages adulthood. develops next caudal ganglionic eminence, which generates inhibitory interneurons, yet most express excitatory markers. In children, cells are (DCX+PSA-NCAM+), adolescence many transition into mature...
We demonstrate that cortical interneurons derived from ventral eminences, including the caudal ganglionic eminence, undergo programmed cell death. Moreover, with exception of VIP interneurons, this occurs in a manner is activity-dependent. In addition, we that, within Calcineurin, calcium-dependent protein phosphatase, plays critical role sequentially linking activity to maturation (E15–P5) and survival (P5–P20). Specifically, embryonic inactivation Calcineurin results failure...
The development of the human neocortex is a highly dynamic process and involves complex cellular trajectories controlled by cell-type-specific gene regulation1. Here, we collected paired single-nucleus chromatin accessibility transcriptome data from 38 neocortical samples encompassing both prefrontal cortex primary visual cortex. These span five main developmental stages, ranging first trimester to adolescence. In parallel, performed spatial transcriptomic analysis on subset illustrate...
The human hippocampus and prefrontal cortex play critical roles in learning cognition
Neuronal subtype generation in the mammalian central nervous system is governed by competing genetic programs. The medial ganglionic eminence (MGE) produces two major cortical interneuron (IN) populations, somatostatin (Sst) and parvalbumin (Pvalb), which develop on different timelines. extent to external signals influence these identities remains unclear. Pvalb-positive INs are crucial for circuit regulation but challenging model vitro. We grafted mouse MGE progenitors into diverse 2D 3D...
The classical adherens junction that holds epithelial cells together consists of a protein complex in which members the cadherin family linked to various catenins are principal components. delta-catenin is mammalian brain Armadillo repeat superfamily with sequence similarity p120(ctn). We found can be immunoprecipitated as other components junction, including and beta-catenin, from transfected brain. interaction involves direct contact within highly conserved juxtamembrane region COOH...
Normal brain development requires a series of highly complex and interrelated steps. This process presents many opportunities for errors to occur, which could result in developmental defects the brain, clinically referred as malformations cortical development. The marginal zone Cajal-Retzius cells are key players established early, yet there is little understanding factors resulting disruption types malformation syndromes. We showed previously that treatment with methylazoxymethanol rats...
Abstract To understand how diverse progenitor cells contribute to human neocortex development, we examined forebrain behaviour using timelapse imaging. Here find that cell cycle dynamics of neuroepithelial (NE) differ from radial glial (RG) in both primary tissue and stem cell-derived organoids. NE undergoing proliferative, symmetric divisions retract their basal processes, daughter regrow a new process following cytokinesis. The mitotic retraction the is recapitulated by cerebral organoids...