A5014872117- Retinal Development and Disorders
- Hedgehog Signaling Pathway Studies
- Developmental Biology and Gene Regulation
- T-cell and B-cell Immunology
- Photoreceptor and optogenetics research
- Ocular Disorders and Treatments
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Wnt/β-catenin signaling in development and cancer
- Neurogenesis and neuroplasticity mechanisms
- Axon Guidance and Neuronal Signaling
- Neuroscience and Neural Engineering
- Ocular Oncology and Treatments
- Photochromic and Fluorescence Chemistry
- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Cancer-related gene regulation
- Corneal Surgery and Treatments
- Retinal Diseases and Treatments
- Monoclonal and Polyclonal Antibodies Research
- bioluminescence and chemiluminescence research
- Ubiquitin and proteasome pathways
- Renal and related cancers
University of Toronto
2015-2024
University Health Network
2015-2024
Krembil Research Institute
2016-2024
Canada Research Chairs
2018-2022
Health Net
2022
Krembil Foundation
2016-2021
Liverpool Heart and Chest Hospital
2020
University of Liverpool
2020
Toronto Western Hospital
2015-2019
University of Ottawa
2008-2017
T lymphocyte maturation is dependent on interactions between the cell receptor (TCR) expressed developing thymocyte and intrathymic major histocompatibility complex (MHC)-peptide ligands. The relation peptide-MHC that results in negative or positive selection has not been identified. Here, requirements for of thymocytes expressing a defined transgenic TCR specific viral peptide are studied fetal thymic organ culture. Low concentrations antigen recognized by this can mediate selection,...
ABSTRACT We show that Sonic hedgehog and patched are expressed in adjacent domains the developing mouse retina. Treatment of cultures perinatal retinal cells with amino-terminal fragment protein results an increase proportion incorporate bromodeoxuridine, total cell numbers, rod photoreceptors, amacrine Müller glial cells, suggesting promotes proliferation precursor cells. These finding suggest part a conserved signalling pathway development mammals insects.
Abstract The neuroepithelial layer of the developing eyecup contains multipotential precursor cells that give rise to all neurons and one glial cell type present in adult retina. Patterning within retinal neuroepithelium is regulated by intrinsic as well extrinsic mechanisms. Although identity some signaling molecules regulate development known, function many others, especially members Wnt family, has yet be characterized context development. We undertook a comprehensive situ hybridization...
Sonic hedgehog (Shh) is an indispensable, extrinsic cue that regulates progenitor and stem cell behavior in the developing adult mammalian central nervous system. Here, we investigate link between Shh signaling pathway Hes1, a classical Notch target. We show Shh-driven stabilization of Hes1 independent requires effector Gli2. identify Gli2 as primary mediator this response by showing required for Hh (Hedgehog)-dependent up-regulation Hes1. also using chromatin immunoprecipitation binds to...
The timing of cell cycle exit and temporal changes in the developmental competence precursor cells are key components for establishment normal complement types mammalian retina. identity extrinsic cues that control these processes is largely unknown. We showed previously mouse retina sonic hedgehog (Shh) signalling from retinal ganglion (RGCs) to (RPC) required organization. Here, we show conditional ablation Shh expression peripheral results a depletion RPC pool, owing precocious cell-cycle...
Abstract The utilization of fluorescent reporter transgenes to discriminate donor versus host cells has been a mainstay photoreceptor transplantation research, the assumption being that presence reporter+ in outer nuclear layer (ONL) transplant recipients represents integration photoreceptors. We previously reported GFP+ ONL cone-GFP transplanted retinas exhibited rod-like characteristics, raising possibility GFP signal recipient tissue may not be consequence cell integration. To investigate...
Developing strategies that promote axonal regeneration within the injured CNS is a major therapeutic challenge, as outgrowth potently inhibited by myelin and glial scar. Although can be achieved using genetic deletion of PTEN, negative regulator mTOR pathway, this requires inactivation prior to nerve injury, thus precluding application. Here, we show that, remarkably, fibroblast-derived exosomes (FD exosomes) enable neurite growth on inhibitory proteins. Moreover, demonstrate upon treatment...
Emerging evidence suggests that intracellular molecules and organelles transfer between cells during embryonic development, tissue homeostasis disease. We others recently showed transplanted host photoreceptors engage in bidirectional of material the recipient retina, a process termed (MT). used cell transplantation, advanced imaging approaches, genetic pharmacologic interventions primary culture to characterize elucidate mechanism MT. show MT correlates with donor persistence accumulation...
ABSTRACT Retinal ganglion cell (RGC) axons have been shown to stimulate the proliferation of astrocytes in developing rodent optic nerve, but signals that mediate this effect not identified. The following findings suggest Sonic hedgehog (Shh) is one signals. (1) RGCs express both Shh mRNA and protein, whereas nerve contains protein mRNA. (2) Astrocytes their precursors Hedgehog (Hh) receptor gene Patched (Ptc), suggesting they are being signalled by an Hh protein. (3) Ptc expression greatly...
The development of optic stalk neuroepithelial cells depends on Hedgehog(Hh) signaling, yet the source(s) Hh protein in is unknown. We provide genetic evidence that sonic hedgehog (Shh) from retinal ganglion (RGCs) promotes disc and cells. demonstrate RGCs express Shh soon after differentiation, at close proximity to Shh-expressing upregulate target genes, which suggests they are responding RGC-derived signaling. Conditional ablation Shhin caused a complete loss astrocyte precursor...
The neocortex is comprised of six neuronal layers that are generated in a defined temporal sequence. While extrinsic and intrinsic cues known to regulate the sequential production neocortical neurons, how these factors interact function coordinated manner poorly understood. proneural gene <i>Neurog2</i> expressed progenitors throughout corticogenesis, but only required specify early-born, deep-layer identities. Here, we examined differentiation general particular temporally controlled during...
Mutations in the mitochondrial PTEN-induced kinase 1 (Pink1) gene have been linked to Parkinson disease (PD). Recent reports including our own indicated that ectopic Pink1 expression is protective against toxic insult vitro, suggesting a potential role for endogenous mediating survival. However, of survival, particularly vivo, unclear. To address this critical question, we examined whether down-regulation affects dopaminergic neuron loss following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine...
Chromatin compaction mediates progenitor to post-mitotic cell transitions and modulates gene expression programs, yet the mechanisms are poorly defined. Snf2h Snf2l ATP-dependent chromatin remodelling proteins that assemble, reposition space nucleosomes, robustly expressed in brain. Here we show mice conditionally inactivated for neural progenitors have reduced levels of histone H1 H2A variants compromise fluidity transcriptional programs within developing cerebellum. Disorganized limits...
Hyaluronan (HA) is a major component of the extracellular matrix and particularly attractive for cell-based assays; yet, common crosslinking strategies HA hydrogels are not fully tunable bioorthogonal, result in gels subject to swelling, which affects their physicochemical properties. To overcome these limitations, based on inverse electron-demand Diels–Alder (IEDDA) "click" reaction designed. By two modified components together, as opposed using telechelic components, gelation times fast...
The role of the Wnt[b]/beta-catenin-dependent pathway (canonical Wnt pathway) in context retinal development and homeostasis is largely unknown. This study was undertaken to characterize activation canonical its relevance cell type populations developing adult retina.Tissue from TCF/Lef-LacZ (T-cell-specific transcription factor/lymphoid enhancer-binding factor) transgenic mice used for monitoring pathway. Lithium (Li(+)) treatment applied induce ectopic reporter gene explants. Gene...
In the embryonic kidney, progenitors in metanephric mesenchyme differentiate into specialized renal epithelia a defined sequence characterized by formation of cellular aggregates, conversion polarized and segmentation along proximal-distal axis. This is reiterated throughout development to generate nephrons. Here, we identify global transcriptional programs associated with epithelial differentiation utilizing an organ culture model rat mesenchymal differentiation, which recapitulates...