A5068006897- Retinal Development and Disorders
- Developmental Biology and Gene Regulation
- Zebrafish Biomedical Research Applications
- Retinopathy of Prematurity Studies
- Retinal Diseases and Treatments
- Photoreceptor and optogenetics research
- Advanced Fluorescence Microscopy Techniques
- Axon Guidance and Neuronal Signaling
- Glaucoma and retinal disorders
- Single-cell and spatial transcriptomics
- Cellular transport and secretion
- Retinoids in leukemia and cellular processes
- Cell Image Analysis Techniques
- CRISPR and Genetic Engineering
- Neurobiology and Insect Physiology Research
- Digestive system and related health
- Growth Hormone and Insulin-like Growth Factors
- Virus-based gene therapy research
- RNA Research and Splicing
- interferon and immune responses
- Cell Adhesion Molecules Research
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neural Engineering
- Diet and metabolism studies
- Vitamin D Research Studies
University at Buffalo, State University of New York
2012-2024
Jacobs Institute
2013-2024
New York University
2020
The University of Texas MD Anderson Cancer Center
2001-2017
State University of New York
2015
Roswell Park Comprehensive Cancer Center
2011-2015
New York State College of Agriculture & Life Sciences
2015
Cancer Genetics (United States)
2014-2015
Institut thématique Génétique, génomique et bioinformatique
2014
The University of Texas Health Science Center at Houston
2013
Understanding gene regulatory networks (GRNs) that control neuronal differentiation will provide systems-level perspectives on neurogenesis. We have previously constructed a model for GRN in retinal ganglion cell (RGC) which four hierarchical tiers of transcription factors ultimately the expression downstream terminal genes. Math5 occupies central node hierarchy because it is essential formation RGCs and immediate factor Pou4f2. Based its expression, we also proposed Isl1, LIM-homeodomain...
Significance We show that the onecut transcription factors, Onecut1 and Onecut2, redundantly regulate formation of all four early-born retinal cell types, namely horizontal cells, ganglion cones, amacrine prevent precocious late type, rods. Expression profiling suggests these two factors a shared set downstream genes to maintain competence for early types generation various subtypes cells. This study lays foundation further examination how differentiation in retina, as well central nervous...
As with other retinal cell types, ganglion cells (RGCs) arise from multipotent progenitor (RPCs), and their formation is regulated by a hierarchical gene-regulatory network (GRN). Within this GRN, three transcription factors--atonal homolog 7 (Atoh7), POU domain, class 4, factor 2 (Pou4f2), insulin gene enhancer protein 1 (Isl1)--occupy key node positions at two different stages of RGC development. Atoh7 upstream required for RPCs to gain competence an fate, whereas Pou4f2 Isl1 are...
Abstract Atoh7 has been believed to be essential for establishing the retinal ganglion cell (RGC) lineage, and Pou4f2 Isl1 are known regulate RGC specification differentiation. Here we report our further study of roles these transcription factors. Using bulk RNA-seq, identify genes regulated by three factors, which expand understanding scope downstream events. scRNA-seq on wild-type mutant cells, reveal a transitional state progenitor cells (RPCs) co-marked other different lineages shared...
Many neurodegenerative diseases cause degeneration of specific types neurons. For example, glaucoma leads to death retinal ganglion cells, leaving other neurons intact. Neurons are not regenerated in the adult mammalian central nervous system. However, nonmammalian vertebrates, glial cells spontaneously reprogram into neural progenitors and replace after injury. We have recently developed strategies stimulate regeneration functional mouse retina by overexpressing proneural factor Ascl1...
In mice, Brn3 POU domain transcription factors play essential roles in the differentiation and survival of projection neurons within retina, inner ear, dorsal root trigeminal ganglia. During retinal ganglion cell differentiation, Brn3b is expressed first, followed by Brn3a Brn3c. Targeted deletion Brn3b, but not or Brn3c, leads to a loss most cells before birth. However, as few are still present Brn3b–/– Brn3c may partially compensate for Brn3b. To examine role development, we generated...
Significance The basal ganglia process cortical information that controls purposeful movements and appropriate behavior via the striatopallidal striatonigral pathways. Despite their importance, little is known about developmental mechanisms control formation of these We show here telencephalic progenitors expressing transcription factor Islet1 give rise to neurons this required for normal development pathway. Moreover, mouse mutants exhibit hyperactivity a paradoxical response...
Abstract How the diverse neural cell types emerge from multipotent progenitor cells during central nervous system development remains poorly understood. Recent scRNA-seq studies have delineated developmental trajectories of individual in many systems including retina. Further understanding formation diversity requires knowledge about how epigenetic landscape shifts along lineages and key transcription factors regulate these changes. In this study, we dissect changes early retinal...
Brn3b/Brn-3.2/POU4f2 is a POU domain transcription factor that essential for retinal ganglion cell (RGC) differentiation, axonal outgrowth and survival. Our goal was to establish link between Brn3b the downstream events leading RGC differentiation. We sought determine both number types of genes depend on their expression. RNA probes from wild-type Brn3b-/- E14.5, E16.5 E18.5 mouse retinas were hybridized microarray containing 18,816 retina-expressed cDNAs. At we identified 87 whose...
Horizontal cells are interneurons that synapse with photoreceptors in the outer retina. Their genesis during development is subject to regulation by transcription factors a hierarchical manner. Previously, we showed Onecut 1 (Oc1), an atypical homeodomain factor, expressed developing horizontal (HCs) and retinal ganglion (RGCs) mouse Herein, knocking out <i>Oc1</i> specifically retina, show majority (∼80%) of HCs fail form early development, implying Oc1 essential for HC genesis. However, no...
Our current study focuses on the expression of two members onecut transcription factor family, Onecut1 (Oc1) and Onecut2 (Oc2), in developing mouse retina. By immunofluorescence staining, we found that Oc1 Oc2 had very similar patterns throughout retinal development. Both factors started to be expressed retina at around embryonic day (E) 11.5. At early stages (E11.5 E12.5), they were both neuroblast layer (NBL) ganglion cell (GCL). As development progressed (from E14.5 postnatal [P] 0),...
Precise regulation of gene expression during biological processes, including development, is often achieved by combinatorial action multiple transcription factors. The mechanisms which these factors collaborate are largely not known. We have shown previously that Isl1, a Lim-Homeodomain factor, and Pou4f2, class IV POU domain co-regulate set genes required for retinal ganglion cell (RGC) differentiation. Here we further explore how two interact to precisely regulate RGC development. By GST...
Retinal development occurs in mice between embryonic day E11.5 and post-natal P8 as uncommitted neuroblasts assume retinal cell fates. The genetic pathways regulating are being identified but little is understood about the global networks that link these together or complexity of expressed gene set required to form retina. At E14.5, retina contains mostly newly differentiated neurons. Here we report a sequence analysis an E14.5 cDNA library. To date, have archived 15 268 ESTs annotated 9035,...
Background Visual information is conveyed from the retina to brain via 15–20 Retinal Ganglion Cell (RGC) types. The developmental mechanisms by which RGC types acquire their distinct molecular, morphological, physiological and circuit properties are essentially unknown, but may involve combinatorial transcriptional regulation. Brn3 transcription factors expressed in RGCs early stages, restricted adults distinct, partially overlapping populations of Previously, we described cell autonomous...
The bHLH transcription factor ATOH7 (Math5) is essential for establishing retinal ganglion cell (RGC) fate. However, Atoh7-expressing progenitor cells (RPCs) can give rise to all types, suggesting that other factors are involved in specifying RGCs. basis by which a subpopulation of RPCs commits an RGC fate remains uncertain but critical importance development since RGCs the earliest type differentiate. To better understand regulatory mechanisms leading cell-fate specification, binary genetic...
Regulated retinal ganglion cell (RGC) differentiation and axonal guidance is required for a functional visual system. Homeodomain basic helix loop transcription factors are retinogenesis, as well patterning, maintenance of specific types. We hypothesized that Dlx1/Dlx2 Brn3b homeobox genes function in parallel intrinsic pathways to determine RGC fate generated Dlx1/Dlx2/Brn3b triple knockout mice. A more severe phenotype was found the null retinas than predicted by combining features single...