A5057027392- Neurogenesis and neuroplasticity mechanisms
- Axon Guidance and Neuronal Signaling
- Developmental Biology and Gene Regulation
- Neuroscience and Neuropharmacology Research
- Retinal Development and Disorders
- Traumatic Brain Injury and Neurovascular Disturbances
- Hedgehog Signaling Pathway Studies
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- Neural dynamics and brain function
- Epigenetics and DNA Methylation
- Visual perception and processing mechanisms
- Congenital heart defects research
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Wnt/β-catenin signaling in development and cancer
- Nerve injury and regeneration
- Receptor Mechanisms and Signaling
- Traumatic Brain Injury Research
- Single-cell and spatial transcriptomics
- Neurobiology and Insect Physiology Research
- Trauma and Emergency Care Studies
- Anesthesia and Neurotoxicity Research
Peter Doherty Institute
2024
The University of Melbourne
2024
University of Edinburgh
2014-2023
Simons Initiative for the Developing Brain
2018-2023
Simons Foundation
2018-2021
Discovery Centre
2020
University of Aberdeen
2012-2015
University of Sheffield
2015
Pinderfields Hospital
1979-2012
Australian National University
2002-2012
GABAergic interneurons (GABA, γ-aminobutyric acid) regulate neural-circuit activity in the mammalian cerebral cortex. These cortical are structurally and functionally diverse. Here, we use single-cell transcriptomics to study origins of this diversity mouse. We identify distinct types progenitor cells newborn neurons ganglionic eminences, embryonic proliferative regions that give rise interneurons. precursors show temporally spatially restricted transcriptional patterns lead different...
In the proliferative zone of developing cerebral cortex, multipotential progenitors predominate early in development and divide to increase progenitor pool. As corticogenesis progresses, proportionately fewer are produced and, instead, cell divisions yield higher numbers postmitotic neurones or glial cells. switch from generation that differentiated cells occurs, orientation division alters predominantly symmetrical asymmetrical. It has been hypothesised expand pool, whereas asymmetrical...
Many cerebral cortical neurons and glia are produced by apical progenitors dividing at the ventricular surface of embryonic dorsal telencephalon. Other basal progenitor cells, which derived from progenitors, away surface. The transcription factor Pax6 is expressed in downregulated upregulate Tbr2. Here we show that Pax6(-/-) cells under-represented cortex Pax6(+/+)<-->Pax6(-/-) chimeras early corticogenesis, indicating required for production normal numbers cells. We provide evidence this...
Understanding brain development remains a major challenge at the heart of understanding what makes us human. The neocortex, in evolutionary terms newest part cerebral cortex, is seat higher cognitive functions. Its normal requires production, positioning, and appropriate interconnection very large numbers both excitatory inhibitory neurons. Pax6 one relatively small group transcription factors that exert high-level control cortical development, whose mutation or deletion from developing...
Disrupted-in-Schizophrenia 1 ( DISC1 ) is a strong candidate gene for schizophrenia and other mental disorders. regulates neurodevelopmental processes including neurogenesis, neuronal migration, neurite outgrowth, neurotransmitter signaling. Abnormal morphology cortical architecture are seen in human postmortem brain from patients with schizophrenia. However, the etiology development of these histological abnormalities remain unclear. We analyzed histology two Disc1 mutant mice point...
Genetic loss or pharmacological inhibition of monoamine oxidase A (MAOA) in mice leads to a large increase whole-brain levels serotonin (5-HT). Excess 5-HT mouse neonates prevents the normal barrel-like clustering thalamic axons somatosensory cortex. Projection fields other neuron populations may develop abnormally. In present study, we have analyzed localization immunolabeling developing brain MAOA knock-out mice. We show numerous atypical locations during embryonic and postnatal...
ABSTRACT The cerebral cortex forms by the orderly migration and subsequent differentiation of neuronal precursors generated in proliferative ventricular zone. We studied role transcription factor Pax-6, which is expressed zone, cortical development. Embryos homozygous for a mutation Pax-6 (Small eye; Sey) had abnormalities suggesting defective late-born precursors. When Sey/Sey were transplanted into wild-type embryonic rat cortex, they showed similar integrative, migrational differentiative...
In mammalian species studied to date, the first-born neocortical cells normally form two layers, one above and below cortical plate, called marginal zone (future layer 1) subplate. primates carnivores, many of these die early in postnatal life. Whether this also occurs rodents is highly controversial. study, we injected pregnant mice with bromodeoxyuridine on embryonic days (E) 11-14 label earliest generated cells, examined their fates between birth day 21. At birth, most born 11 were a...
ABSTRACT Pax-6 is one of the earliest regulatory genes to be expressed in diencephalon. We tested whether normal protein required for early diencephalic development by examining morphology, precursor proliferation and patterns gene expression embryonic diencephalon Small-eye mice (Pax-6 mutants). In Smalleye mice, morphology was abnormal at all ages studied (days 10.5, 12.5 14.5). Regional differences cell density were lost, diencephalon/mesencephalon boundary unclear third ventricle...
Pax6 is a developmental control gene with an essential role in development of the eye, brain and pancreas. Pax6, as many other regulators, depends on substantial number cis-regulatory elements addition to its promoters for correct spatiotemporal quantitative expression. Here we report our analysis set mice transgenic modified yeast artificial chromosome carrying human PAX6 locus. In this 420 kb YAC tauGFP-IRES-Neomycin reporter cassette has been inserted into translational start site exon 4....
Genetic inactivation of monoamine oxidase A (MAOA) in C3H/HeJ mice causes a complete absence barrels the somatosensory cortex, and similar alterations are caused by pharmacological inhibition MAOA wild type mice. To determine when how affects development barrel field, inhibitor clorgyline was administered to outbred strain OF1 for various time periods between embryonic day 15 (E15) postnatal 7 (P7), fields were analyzed with cytochrome Nissl stains P10 adult High-pressure liquid...
We describe an investigation into the pattern dependence of dishing and erosion during chemical‐mechanical polishing copper used for delineating inlaid metal patterns. Copper is determined to be highly dependent on width structure, but only minimally density structures. Erosion dielectric layer strongly affected by density, not changes in lines. As a result, both line are important considerations predicting final thickness
Retinal ganglion cell (RGC) axons from each eye execute a series of maneuvers as they converge on the ventral surface brain at optic chiasm for sorting into tracts. Heparan sulfate proteoglycans (HSPGs) are extracellular glycoproteins involved in cell-surface interactions. HSPGs exhibit massive structural diversity, conferred partly by extensive post-translational modification including differential sulfation. Here we examine roles HSPG sulfation RGC axon guidance chiasm. We identified...
Levels of expression the transcription factor Pax6 vary throughout corticogenesis in a rostro-lateralhigh to caudo-mediallow gradient across cortical proliferative zone. Previous loss-of-function studies have indicated that is required for normal progenitor proliferation, neuronal differentiation, lamination and arealization, but whether how its level affects function unclear. We studied developing cortex PAX77 YAC transgenic mice carrying several copies human PAX6 locus with full complement...
Cerebral cortical neurons arise from radial glia (direct neurogenesis) or intermediate progenitors (indirect neurogenesis); intriguingly, the sizes of progenitor populations and cortices they generate correlate across species. The generation is regulated by transcription factor Tbr2, whose expression marks these cells. We investigated how this mechanism might be controlled. found that acute blockade mature microRNA biosynthesis in murine caused a rapid cell autonomous increase numbers...