A5074520935- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Neuroscience and Neural Engineering
- Axon Guidance and Neuronal Signaling
- MicroRNA in disease regulation
- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- Neuroscience and Neuropharmacology Research
- Glaucoma and retinal disorders
- Italian Fascism and Post-war Society
- CRISPR and Genetic Engineering
- Nerve injury and regeneration
- Developmental Biology and Gene Regulation
- Zebrafish Biomedical Research Applications
- Educational and Social Studies
- Ubiquitin and proteasome pathways
- Protein Kinase Regulation and GTPase Signaling
- Mitochondrial Function and Pathology
- Horticultural and Viticultural Research
- Microtubule and mitosis dynamics
- Chemokine receptors and signaling
- Diverse academic and cultural studies
- Signaling Pathways in Disease
- Genetics and Neurodevelopmental Disorders
- melanin and skin pigmentation
University of California, Davis
2016-2025
University of Wisconsin–Madison
2018
New York University
2018
University of Oxford
2018
University College London
2018
Wellcome Trust Centre for the History of Medicine
2018
Burroughs Wellcome Fund
2018
Health and Human Development (2HD) Research Network
2018
Universitat de Barcelona
2004-2017
University of Washington
2012-2017
Significance The sequential generation of different types neurons and glia is a fundamental property neurogenesis, but little known about the mechanisms controlling this phenomenon. Conditional deletion Dicer prevents progenitors from progressing in their competence to generate late cell types, indefinitely generating early types. We now elucidate molecular mechanism for Three microRNAs, let-7, microRNA-125, microRNA-9, serve as key regulators developmental transition retinal progenitors....
Previous studies have demonstrated the ability of retinal cells derived from human embryonic stem (hESCs) to survive, integrate into host retina, and mediate light responses in murine mouse models. Our aim is determine whether these can also survive retina a nonhuman primate, Saimiri sciureus, following transplantation subretinal space.hESCs were differentiated toward neuronal fates using our previously published technique cultured for 60 70 days. Differentiated further treated with 20 μM...
The brain, spinal cord, and neural retina comprise the central nervous system (CNS) of vertebrates. Understanding regulatory mechanisms that underlie enormous cell-type diversity CNS is a significant challenge. Whole-genome mapping DNase I-hypersensitive sites (DHSs) has been used to identify cis-regulatory elements in many tissues. We have applied this approach mouse CNS, including developing mature retina, whole two well-characterized brain regions, cerebellum cerebral cortex.For various...
Chronic neurodegeneration and acute injuries lead to neuron losses via diverse processes. We compared retinal ganglion cell (RGC) responses between chronic glaucomatous conditions the injury model. Among major RGC subclasses, αRGCs intrinsically photosensitive RGCs (ipRGCs) preferentially survive conditions, similar findings in retina subject axotomy. Focusing on an αRGC intrinsic factor, Osteopontin (secreted phosphoprotein 1 [Spp1]), we found ectopic neuronal expression of (Spp1) other...
Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, the molecular mechanisms underlying neurodegeneration unknown. We find that OPTN C-terminus truncation (OPTN∆C) causes late-onset of retinal ganglion cells (RGCs), optic nerve (ON), spinal cord motor neurons, preceded by decrease axonal mitochondria in mice. discover directly interacts with both microtubules mitochondrial transport complex...
The signaling cascades governing neuronal migration are believed to link extracellular signals cytoskeletal components. MAP1B is a neuron-specific microtubule-associated protein implicated in the control of dynamic stability microtubules and cross-talk between actin filaments. Here we show that Reelin can induce mode I phosphorylation, both vivo vitro, through gsk3 cdk5 activation. Additionally, mDab1 participates cascade responsible for phosphorylation. Conversely, MAP1B-deficient mice...
Abstract In the neural progenitors of developing central nervous system (CNS), cell proliferation is tightly controlled and coordinated with fate decisions. Progenitors divide rapidly during early development their cycle lengthens progressively as advances to eventually give rise a tissue correct size cellular composition. However, our understanding molecules linking progression developmental time incomplete. Here, we show that microRNA (miRNA) let-7 accumulates in over throughout CNS....
Neurons use cell-adhesion molecules (CAMs) to interact with other neurons and the extracellular environment: combination of CAMs specifies migration patterns, neuronal morphologies, synaptic connections across diverse neuron types. Yet little is known regarding intracellular signaling cascade mediating CAM recognitions at cell surface different In this study, we investigated neural developmental role Afadin 1–4 , a cytosolic adapter protein that connects multiple families F-actin. We...
Neurons use cell-adhesion molecules (CAMs) to interact with other neurons and the extracellular environment: combination of CAMs specifies migration patterns, neuronal morphologies, synaptic connections across diverse neuron types. Yet little is known regarding intracellular signaling cascade mediating CAM recognitions at cell surface different In this study, we investigated neural developmental role Afadin 1–4 , a cytosolic adapter protein that connects multiple families F-actin. We...
Reelin binds to very low–density lipoprotein receptor and apolipoprotein E 2, thereby inducing mDab1 phosphorylation activation of the phosphatidylinositide 3 kinase (PI3K) pathway. Here we demonstrate that activates mitogen-activated protein kinase/extracellular signal-regulated (ERK) pathway, which leads Erk1/2 proteins. The inhibition Src family kinases (SFK) blocked Reelin-dependent activation. This was also shown in neuronal cultures from mDab1-deficient mice. Although rat sarcoma viral...
Axon injury is a hallmark of many neurodegenerative diseases, often resulting in neuronal cell death and functional impairment. Dual leucine zipper kinase (DLK) has emerged as key mediator this process. However, while DLK inhibition robustly protective wide range disease models, it also inhibits axonal regeneration. Indeed, there are no genetic perturbations that known to both improve long-term survival promote To identify such neuroprotective target, we conducted set complementary...
Interaction between tumor cells and stroma is essential for growth. Tumor stimulate the formation of stromal tissue, which excretes a variety growth factors, cytokines, proteases. Tumor-associated macrophages (TAMs) are one major components tissue capable eliciting diverse aspects as either positive or negative regulator (1). In breast carcinoma, large numbers infiltrating T TAMs often observed. The leukocyte infiltrate found within areas well in epithelial that constitute mass...
Abstract Neural cell adhesion molecule 2 (NCAM2) is involved in the development and plasticity of olfactory system. Genetic data have implicated NCAM2 gene neurodevelopmental disorders including Down syndrome autism, although its role cortical unknown. Here, we show that while overexpression hippocampal neurons leads to minor alterations, downregulation severely compromises dendritic architecture, leading an aberrant phenotype shorter trees, retraction dendrites, emergence numerous somatic...
Neurotrophins are involved in many crucial cellular functions, including neurite outgrowth, synapse formation, and plasticity. Although these events have long been known, the molecular determinants underlying neuritogenesis not fully characterized. Ack1 (activated Cdc42-associated tyrosine kinase) is a non-receptor kinase that highly expressed brain. Here, we demonstrate constituent of neurotrophin signaling cascades neurons PC12 cells. We report interacts with Trk receptors becomes...
Retinal neurons, particularly retinal ganglion cells (RGCs), are susceptible to the degenerative damage caused by different inherited conditions and environmental insults, leading irreversible vision loss and, ultimately, blindness. Numerous strategies being tested in models of degeneration restore recent years, stem cell technologies have offered novel avenues obtain donor for replacement therapies. To date, cell–based transplantation retina has been attempted as treatment photoreceptor...