A5013652397- Neurogenesis and neuroplasticity mechanisms
- Immunotherapy and Immune Responses
- Zebrafish Biomedical Research Applications
- Developmental Biology and Gene Regulation
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Amyotrophic Lateral Sclerosis Research
- Retinoids in leukemia and cellular processes
- Neurogenetic and Muscular Disorders Research
- Histone Deacetylase Inhibitors Research
- Alzheimer's disease research and treatments
- Extracellular vesicles in disease
- Axon Guidance and Neuronal Signaling
- RNA Research and Splicing
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Congenital heart defects research
- Signaling Pathways in Disease
- Genomics and Chromatin Dynamics
- Neuroinflammation and Neurodegeneration Mechanisms
- Angiogenesis and VEGF in Cancer
- Neuroscience and Neuropharmacology Research
- Cancer-related gene regulation
- Phosphodiesterase function and regulation
- Cholinesterase and Neurodegenerative Diseases
- Redox biology and oxidative stress
Johns Hopkins University
2015-2024
Johns Hopkins Medicine
2015-2024
Medical Research Council
1992-2012
Kings Health Partners
2012
University of Oslo
2012
Dartmouth College
2012
University of California, Berkeley
2012
Howard Hughes Medical Institute
1998-2003
Columbia University
1997-2003
Osaka University
1995
The homeobox gene Hb9, like its close relative MNR2, is expressed selectively by motor neurons (MNs) in the developing vertebrate CNS. In embryonic chick spinal cord, ectopic expression of MNR2 or Hb9 sufficient to trigger MN differentiation and repress an adjacent population V2 interneurons. Here, we provide genetic evidence that has essential role differentiation. mice lacking function, MNs are generated on schedule normal numbers but transiently acquire molecular features aberrant...
ABSTRACT The Sox gene family consists of a large number embryonically expressed genes related via the possession 79-amino-acid DNA-binding domain known as HMG box. Partial clones for first three (a1-a3) were isolated by homology to box testis-determining Sry and are now termed Sox-1, Sox-2 Sox-3. Sox-3 is highly conserved amongst mammalian species located on X chromosome. This has led proposal that evolved from We present cloning sequencing mouse show most closely Sry. also confirm...
The protein encoded by the human testis determining gene, SRY, contains a high mobility group (HMG) box related to that present in T cell-specific, DNA-binding TCF-1. Recombinant SRY was able bind same core sequence AACAAAG recognized TCF-1 dependent manner. In five XY females point mutations were found region encoding HMG box. four cases DNA binding activity of mutant negligible; fifth case reduced. These results imply is required for sex determination.
The diversification of neuronal cell types in the vertebrate central nervous system depends on inductive signals provided by local organizing groups both neural and nonneural origin. influence postmitotic neurons fate born at subsequent development stages, however, remains unclear. We provide evidence that a retinoid-mediated signal one subset early-born spinal motor imposes variation number generated different axial levels also specifies identity later-born neurons. Thus, distinct fates...
It is known that vitamin A and its metabolite, retinoic acid (RA), are essential for host defense. However, the mechanisms how RA controls inflammation incompletely understood. The findings presented in this study show signaling occurs concurrent with development of inflammation. In models vaccination allogeneic graft rejection, whole body imaging reveals temporally spatially restricted to site Conditional ablation T cells significantly interferes CD4+ cell effector function, migration,...
The six-transmembrane protein glycerophosphodiester phosphodiesterase 2 (GDE2) induces spinal motor neuron differentiation by inhibiting Notch signaling in adjacent progenitors. GDE2 function requires activity of its extracellular domain that shares homology with phosphodiesterases (GDPDs). GDPDs metabolize glycerophosphodiesters into glycerol-3-phosphate and corresponding alcohols, but whether inhibits this mechanism is unclear. Here, we show GDE2, unlike classical GDPDs, cleaves...
Abstract Brain development requires a fine-tuned copper homoeostasis. Copper deficiency or excess results in severe neuro-pathologies. We demonstrate that upon neuronal differentiation, cellular demand for increases, especially within the secretory pathway. flow to this compartment is facilitated through transcriptional and metabolic regulation. Quantitative real-time imaging revealed gradual change oxidation state of cytosolic glutathione differentiation. Transition from broad range redox...
ABSTRACT The response to neural induction depends on the presence of inducing signals and state competence responding tissue. epiblast chick embryo loses its ability respond by organizer (Hensen’s node) between stages 4 4+. We find that pattern expression L5220 antigen closely mirrors changes in time space. For first time, we describe an experiment can extend period competence: when is maintained beyond normal implanting HGF/SF secreting cells, Hensen’s node grafts retained. host forms a...
Semaphorins are a large family of axon guidance molecules that known primarily as ligands for plexins and neuropilins. Although class-6 semaphorins transmembrane proteins, they have been implicated in different aspects neural development, including crest cell migration, cerebellar development. However, the specific spatial temporal expression semaphorin 6B (Sema6B) chick commissural neurons suggested receptor role at spinal cord midline. Indeed, absence Sema6B, post-crossing axons lacked an...
Neurons and oligodendrocytes communicate to regulate oligodendrocyte development ensure appropriate axonal myelination. Here, we show that Glycerophosphodiester phosphodiesterase 2 (GDE2) signaling underlies a neuronal pathway promotes maturation through the release of soluble neuronally derived factors. Mice lacking global or GDE2 expression have reduced mature myelin proteins but retain normal numbers precursor cells (OPCs). Wild-type (WT) OPCs cultured in conditioned medium (CM) from...
Vitamin A is a dietary component that essential for the development of intestinal immunity. absorbed and converted to its bioactive derivatives retinol retinoic acid by epithelium, yet little known about how epithelial cells regulate vitamin A-dependent Here we show cell expression transcription factor receptor β (RARβ) Epithelial RARβ activated serum amyloid (SAA) proteins binding directly Saa promoters. In accordance with role SAAs in regulating Th17 effector function, promoted IL-17...
Abstract Background Alzheimer’s disease (AD) and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) are debilitating neurodegenerative diseases for which there currently no cures. Familial cases with known genetic causes make up less than 10% of these diseases, little is about the underlying mechanisms that contribute to sporadic disease. Accordingly, it important expand investigations into possible pathways may pathophysiology. Glycerophosphodiester phosphodiesterase 2 (GDE2 or...
During neural development, coordinate regulation of cell-cycle exit and differentiation is essential for cell-fate specification, cell survival, proper wiring neuronal circuits. However, the molecules that direct these events remain poorly defined. In developing spinal cord, motor neuron progenitors into postmitotic neurons regulated by retinoid signaling. Here, we identify a retinoid-inducible gene, GDE2 (glycerophosphodiester phosphodiesterase 2), encoding six-transmembrane protein...
Abstract Neural progenitors and terminally differentiated neurons show distinct redox profiles, suggesting that coupled-redox cascades regulate the initiation progression of neuronal differentiation. Discrete cellular compartments have different environments how they contribute to differentiation is unclear. Here we Prdx4, an endoplasmic reticulum (ER) enzyme metabolizes H 2 O , acts as a tunable regulator neurogenesis via its compartmentalized thiol-oxidative function. Prdx4 ablation causes...
A disintegrin and metalloprotease 10 (ADAM10) is the α-secretase for amyloid precursor protein (APP). ADAM10 cleaves APP to generate neuroprotective soluble APPα (sAPPα), which precludes generation of Aβ, a defining feature Alzheimer's disease (AD) pathophysiology. Reduced activity implicated in AD, but mechanisms mediating modulation are unclear. We find that plasma membrane enzyme glycerophosphodiester phosphodiesterase 2 (GDE2) stimulates cleavage by shedding inactivating...