A5068357388- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Neuroscience and Neuropharmacology Research
- Neurobiology and Insect Physiology Research
- Axon Guidance and Neuronal Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Receptor Mechanisms and Signaling
- Retinopathy of Prematurity Studies
- Zebrafish Biomedical Research Applications
- Neurogenesis and neuroplasticity mechanisms
- Neonatal and fetal brain pathology
- Retinoids in leukemia and cellular processes
- Retinal Diseases and Treatments
- Immune cells in cancer
- CRISPR and Genetic Engineering
- Drug-Induced Ocular Toxicity
- Advanced Fluorescence Microscopy Techniques
- Nerve injury and regeneration
- Neonatal Respiratory Health Research
- Immune Response and Inflammation
- Hearing, Cochlea, Tinnitus, Genetics
- Glaucoma and retinal disorders
- RNA regulation and disease
- Cellular transport and secretion
- Folate and B Vitamins Research
Duke University
2016-2025
Duke University Hospital
2019
Duke Medical Center
2019
Institute of Neurobiology
2017
Harvard University
2009-2013
University of California, San Francisco
2001-2005
Icahn School of Medicine at Mount Sinai
2000
Columbia University
1999
The retina contains ganglion cells (RGCs) that respond selectively to objects moving in particular directions. Individual members of a group ON-OFF direction-selective RGCs (ooDSGCs) detect stimuli one four directions: ventral, dorsal, nasal, or temporal. Despite this physiological diversity, little is known about subtype-specific differences structure, molecular identity, and projections. To seek such differences, we characterized mouse transgenic lines mark ooDSGCs preferring ventral nasal...
The visual system converts the distribution and wavelengths of photons entering eye into patterns neuronal activity, which then drive motor endocrine behavioral responses. gene products important for processing by a living behaving vertebrate animal have not been identified in an unbiased fashion. Likewise, genes that affect development nervous to shape function later life are largely unknown. Here we set out close this gap our understanding using forward genetic approach zebrafish. Moving...
The mammalian retina contains six major cell types, several of which are divided into multiple molecularly and morphologically distinct subtypes. To understand how subtype diversity arises during development, we focused on amacrine interneurons in the mouse retina; approximately 30 subtypes have been identified mammals. We used antibody markers to identify two main subsets--GABAergic glycinergic--and further subdivided these groups smaller subsets based expression neurotransmitter...
Abstract Genes encoding cell-surface proteins control nervous system development and are implicated in neurological disorders. These genes produce alternative mRNA isoforms which remain poorly characterized, impeding understanding of how disease-associated mutations cause pathology. Here we introduce a strategy to define complete portfolios full-length encoded by individual genes. Applying this approach neural molecules, identify thousands unannotated expressed retina brain. By mass...
Abstract Müller glia, the most abundant glia of vertebrate retina, have an elaborate morphology characterized by a vertical stalk that spans retina and branches in each retinal layer. play diverse, critical roles homeostasis, which are presumably enabled their complex anatomy. However, much remains unknown, particularly mouse, about anatomical arrangement cells arbors, how these features arise development. Here we use membrane‐targeted fluorescent proteins to reveal fine structure mouse...
Naturally occurring cell death is a fundamental developmental mechanism for regulating numbers and sculpting developing organs. This particularly true in the nervous system, where large of neurons oligodendrocytes are eliminated via apoptosis during normal development. Given profound impact upon these two major populations, it surprising that another type—the astrocyte—has rarely been studied. It presently unclear whether astrocytes subject to significant death, if so, how occurs. Here, we...
Abstract Immature astrocytes and blood vessels enter the developing mammalian retina at optic nerve head migrate peripherally to colonize entire retinal fiber layer (RNFL). Retinal vascularization is arrested in retinopathy of prematurity (ROP), a major cause bilateral blindness children. Despite their importance normal development ROP, factors that control remain poorly understood. Because form reticular network appears provide substrate for migrating endothelial cells, they have long been...
A common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how arise during neurodevelopment remains unknown. Here, we identify the earliest events that initiate formation of direction-selective circuit in inner plexiform layer mouse retina. We demonstrate radially migrating newborn starburst amacrine cells establish homotypic...
In the developing nervous system, progenitor cells must decide when to withdraw from cell cycle and commence differentiation. There is considerable debate whether cell-extrinsic or cell-intrinsic factors are most important for triggering this switch. vertebrate retina, initiation of neurogenesis has recently been explained by a `sequential-induction' model– signals newly differentiated neurons thought trigger in adjacent progenitors, creating wave that spreads across retina stereotypical...
The inner plexiform layer (IPL) of the vertebrate retina comprises functionally specialized sublaminae, representing connections between bipolar,amacrine and ganglion cells with distinct visual functions. Developmental mechanisms that target neurites to correct synaptic sublaminae are largely unknown. Using transgenic zebrafish expressing GFP in subsets amacrine cells, we imaged IPL formation sublamination vivo asked whether major postsynaptic this circuit, organize presynaptic inputs. We...
In the inner plexiform layer (IPL) of mouse retina, ~70 neuronal subtypes organize their neurites into an intricate laminar structure that underlies visual processing. To find recognition proteins involved in lamination, we utilized microarray data from 13 to identify differentially-expressed extracellular and performed a high-throughput biochemical screen. We identified ~50 previously-unknown receptor-ligand pairs, including new interactions among members FLRT Unc5 families. These show...
The retina contains two populations of cholinergic amacrine cells, one positioned in the ganglion cell layer (GCL) and other inner nuclear (INL), that together comprise ∼1/2 a percent all retinal neurons. present study examined genetic control number distribution between these layers. total cells was quantified C57BL/6J A/J inbred mouse strains, 25 recombinant strains derived from them, variations their ratio (GCL/INL) across were mapped to genomic loci. found vary 27,000 40,000 despite...
Loss-of-function mutations in MEGF10 lead to a rare and understudied neuromuscular disorder known as MEGF10-related myopathy. There are no treatments for the progressive respiratory distress, motor impairment, structural abnormalities muscles caused by loss of function. In this study, we deployed cellular molecular assays obtain additional insights about myopathy juvenile, young adult, middle-aged Megf10 knockout (KO) mice. We found fewer muscle fibers juvenile adult KO mice, supporting...
ABSTRACT Background and Aims At the neuromuscular junction (NMJ), synapse between motor neurons muscle fibers, reside perisynaptic Schwann cells (PSCs) which are specialized glia that regulate maintenance repair of this synapse. While we know how PSC morphology numbers change in aging various disorders adversely affect NMJ, molecular mechanisms alter functions remain unknown. In study, investigated whether MEGF10 PSCs modulates NMJ stability developing, healthy young adult, middle‐aged,...
In response to injury, progenitor cells in the adult brain can proliferate and generate new neurons and/or glia, which may then participate injury-induced compensatory processes. this study, we explore ability of young mice 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions, selectively kill nigrostriatal dopaminergic neurons. Using thymidine analogue 5-bromo-2′-deoxyuridine (BrdU), labeled dividing 3, 10, 15 days after MPTP lesion. A robust proliferative was seen specifically...