A5058672711- Genetics and Neurodevelopmental Disorders
- Neurogenesis and neuroplasticity mechanisms
- Autism Spectrum Disorder Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Mitochondrial Function and Pathology
- Congenital heart defects research
- RNA regulation and disease
- Axon Guidance and Neuronal Signaling
- Epigenetics and DNA Methylation
- Genetic Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Glioma Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
- Ubiquitin and proteasome pathways
- Neural dynamics and brain function
- MicroRNA in disease regulation
- Nerve injury and regeneration
- Obsessive-Compulsive Spectrum Disorders
- Spinal Cord Injury Research
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Functional Brain Connectivity Studies
- Immune cells in cancer
- Genomic variations and chromosomal abnormalities
- Fetal and Pediatric Neurological Disorders
University of California, Davis
2015-2024
University of California Davis Medical Center
2016-2024
Shriners Hospitals for Children - Northern California
2015-2024
Shriners Hospitals for Children
2016-2024
Shriners Hospitals for Children - Erie
2010-2024
California Institute for Regenerative Medicine
2008-2020
University of California, San Francisco
2006-2019
Broad Center
2010
Universidad Autónoma de Madrid
2002-2007
Columbia University
2004
Neurogenesis must be properly regulated to ensure that cell production does not exceed the requirements of growing cerebral cortex, yet our understanding mechanisms restrain neuron remains incomplete. We investigated function microglial cells in developing cortex prenatal and postnatal macaques rats show microglia limit cortical neurons by phagocytosing neural precursor cells. selectively colonize proliferative zones phagocytose as neurogenesis nears completion. found deactivating utero with...
Abstract Neocortical precursor cells undergo symmetric and asymmetric divisions while producing large numbers of diverse cortical cell types. In Drosophila , cleavage plane orientation dictates the inheritance fate‐determinants symmetry newborn daughter during neuroblast divisions. One model for predicting fate in mammalian neocortex is also based on orientation. Precursor with a that perpendicular respect to ventricular surface (vertical) are predicted be symmetric, parallel (horizontal)...
The cognitive phenotype of autism has been correlated with an altered balance excitation to inhibition in the cerebral cortex, which could result from a change number, function, or morphology GABA-expressing interneurons. number GABAergic interneuron subtypes not quantified autistic cortex. We classified interneurons into 3 subpopulations based on expression calcium-binding proteins parvalbumin, calbindin, calretinin. each subtype postmortem neocortical tissue 11 cases and 10 control cases....
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by limited expansion of CGG repeats in the 5′ UTR FMR1. Two mechanisms are proposed to cause FXTAS: RNA gain-of-function, where sequesters specific proteins, and translation into polyglycine-containing protein, FMRpolyG. Here we developed transgenic mice expressing repeat with or without Expression FMRpolyG pathogenic, while sole expression not. interacts nuclear lamina protein LAP2β disorganizes...
The vertebrate cerebral cortex varies from the 3-layered dorsal of reptiles to 6-layered lissencephalic characteristic rodents and gyrencephalic typical carnivores primates. Distinct developmental mechanisms may have evolved independently account for radial expansion that produced multilayered mammals tangential cortical surface area resulted in cortex. Recent evidence shows during late stages development, glial cells divide asymmetrically ventricular zone generate intermediate progenitor...
The mammalian cerebral cortex arises from precursor cells that reside in a proliferative region surrounding the lateral ventricles of developing brain. Recent work has shown subventricular zone (SVZ) provide major contribution to prenatal cortical neurogenesis, and SVZ is significantly thicker gyrencephalic mammals such as primates than it lissencephalic including rodents. Identifying characteristics are shared by or distinguish across species will shed light on factors regulate neurogenesis...
Gut microbiota has the capacity to impact regular function of brain, which can in turn affect composition microbiota. Autism spectrum disorder (ASD) patients suffer from gastrointestinal problems and experience changes gut microbiota; however, it is not yet clear whether change associated with ASD a cause or consequence disease.
Changes in the function of inhibitory interneurons (INs) during cortical development could contribute to pathophysiology neurodevelopmental disorders. Using all-optical vivo approaches, we find that parvalbumin (PV) INs and their immature precursors are hypoactive transiently decoupled from excitatory neurons postnatal mouse somatosensory cortex (S1) Fmr1 KO mice, a model fragile X syndrome (FXS). This leads loss (PV-INs) both mice humans with FXS. Increasing activity future PV-INs neonatal...
Abstract Reelin, a large extracellular matrix glycoprotein, is secreted by several neuron populations in the developing and adult rodent brain. Secreted Reelin triggers complex signaling pathway binding lipoprotein integrin membrane receptors target cells. regulates migration dendritic growth neurons, while it can modulate synaptic plasticity neurons. To identify which neural circuits be modulated Reelin‐mediated signaling, we systematically mapped distribution of rat brain using sensitive...
Abstract An interneuron alteration has been proposed as a source for the modified balance of excitation / inhibition in cerebral cortex autism. We previously demonstrated decreased number parvalbumin (PV)-expressing interneurons prefrontal PV-expressing include chandelier (Ch) and basket (Bsk) cells. asked whether PV+ affected both Ch cells Bsk The lack single markers to specifically label or presented an obstacle addressing this question. devised method discern between PV-Ch PV-Bsk based on...
Abstract Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with premutation repeat expansion (55–200 CGG repeats) in the 5′ noncoding region of FMR1 gene. Solitary intranuclear inclusions within FXTAS neurons and astrocytes constitute hallmark disorder, yet our understanding how why these bodies form limited. Here, we have discovered that emit distinct autofluorescence spectrum, which forms basis novel, unbiased method for isolating by preparative...
Interlaminar astrocytes (ILAs) are a subset of cortical that reside in layer I, express GFAP, have soma contacting the pia, and contain long interlaminar processes extend through several layers. We studied prenatal postnatal development ILAs three species primates (rhesus macaque, chimpanzee, human). found generated prenatally likely from radial glial (RG) cells, proliferate locally during gestation, stages development. showed density morphological complexity increase with age, multiple...
Transcriptional silencing of the FMR1 gene in fragile X syndrome (FXS) leads to loss RNA-binding protein FMRP. In addition regulating mRNA translation and synthesis, emerging evidence suggests that FMRP acts coordinate proliferation differentiation during early neural development. However, whether FMRP-mediated translational control is related impaired cell fate specification developing human brain remains unknown. Here, we use patient induced pluripotent stem (iPSC)-derived progenitor cells...