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638 results on '"Nathans, Jeremy"'

2. Peropsin modulates transit of vitamin A from retina to retinal pigment epithelium

Author

Cook, Jeremy D, Ng, Sze Yin, Lloyd, Marcia, Eddington, Shannan, Sun, Hui, Nathans, Jeremy, Bok, Dean, Radu, Roxana A, and Travis, Gabriel H

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Eye Disease and Disorders of Vision, Genetics, Neurosciences, 1.1 Normal biological development and functioning, Underpinning research, Aetiology, 2.1 Biological and endogenous factors, Eye, Animals, Eye Proteins, Mice, Mice, Knockout, Retina, Retinal Cone Photoreceptor Cells, Retinal Pigment Epithelium, Retinal Pigments, Retinaldehyde, Retinoids, Retinol-Binding Proteins, Retinol-Binding Proteins, Cellular, Rhodopsin, Rod Opsins, Vitamin A, G protein-coupled receptor, gene knock-out, membrane, photoreceptor, retina, retinal metabolism, retinoid-binding protein, retinol, vitamin A, Chemical Sciences, Biological Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences
Abstract

Peropsin is a non-visual opsin in both vertebrate and invertebrate species. In mammals, peropsin is present in the apical microvilli of retinal pigment epithelial (RPE) cells. These structures interdigitate with the outer segments of rod and cone photoreceptor cells. RPE cells play critical roles in the maintenance of photoreceptors, including the recycling of visual chromophore for the opsin visual pigments. Here, we sought to identify the function of peropsin in the mouse eye. To this end, we generated mice with a null mutation in the peropsin gene (Rrh). These mice exhibited normal retinal histology, normal morphology of outer segments and RPE cells, and no evidence of photoreceptor degeneration. Biochemically, Rrh-/- mice had ∼2-fold higher vitamin A (all-trans-retinol (all-trans-ROL)) in the neural retina following a photobleach and 5-fold lower retinyl esters in the RPE. This phenotype was similar to those reported in mice that lack interphotoreceptor retinoid-binding protein (IRBP) or cellular retinol-binding protein, suggesting that peropsin plays a role in the movement of all-trans-ROL from photoreceptors to the RPE. We compared the phenotypes in mice lacking both peropsin and IRBP with those of mice lacking peropsin or IRBP alone and found that the retinoid phenotype was similarly severe in each of these knock-out mice. We conclude that peropsin controls all-trans-ROL movement from the retina to the RPE or may regulate all-trans-ROL storage within the RPE. We propose that peropsin affects light-dependent regulation of all-trans-ROL uptake from photoreceptors into RPE cells through an as yet undefined mechanism.

Published
2017

5. Epigenomic landscapes of retinal rods and cones.

Author

Mo, Alisa, Luo, Chongyuan, Davis, Fred P, Mukamel, Eran A, Henry, Gilbert L, Nery, Joseph R, Urich, Mark A, Picard, Serge, Lister, Ryan, Eddy, Sean R, Beer, Michael A, Ecker, Joseph R, and Nathans, Jeremy

Subjects
Animals, Mice, Histones, Transcription Factors, DNA, Gene Expression Profiling, Epigenesis, Genetic, Methylation, Retinal Rod Photoreceptor Cells, Retinal Cone Photoreceptor Cells, DNA methylation, chromatin, evolutionary biology, genomics, mouse, neuroscience, retinal development, retinal photoreceptors, transcription factors, Epigenesis, Genetic, Biochemistry and Cell Biology
Abstract

Rod and cone photoreceptors are highly similar in many respects but they have important functional and molecular differences. Here, we investigate genome-wide patterns of DNA methylation and chromatin accessibility in mouse rods and cones and correlate differences in these features with gene expression, histone marks, transcription factor binding, and DNA sequence motifs. Loss of NR2E3 in rods shifts their epigenomes to a more cone-like state. The data further reveal wide differences in DNA methylation between retinal photoreceptors and brain neurons. Surprisingly, we also find a substantial fraction of DNA hypo-methylated regions in adult rods that are not in active chromatin. Many of these regions exhibit hallmarks of regulatory regions that were active earlier in neuronal development, suggesting that these regions could remain undermethylated due to the highly compact chromatin in mature rods. This work defines the epigenomic landscapes of rods and cones, revealing features relevant to photoreceptor development and function.

Published
2016

9. Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain

Author

Mo, Alisa, Mukamel, Eran A, Davis, Fred P, Luo, Chongyuan, Henry, Gilbert L, Picard, Serge, Urich, Mark A, Nery, Joseph R, Sejnowski, Terrence J, Lister, Ryan, Eddy, Sean R, Ecker, Joseph R, and Nathans, Jeremy

Subjects
Genetics, Biotechnology, Human Genome, Neurosciences, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Animals, Cell Nucleolus, Chromatin Immunoprecipitation, DNA Methylation, Epigenomics, Gene Expression Profiling, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Mice, Mice, Transgenic, Microtubule-Associated Proteins, Neocortex, Nerve Tissue Proteins, Neurons, Proto-Oncogene Proteins c-myc, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Neuronal diversity is essential for mammalian brain function but poses a challenge to molecular profiling. To address the need for tools that facilitate cell-type-specific epigenomic studies, we developed the first affinity purification approach to isolate nuclei from genetically defined cell types in a mammal. We combine this technique with next-generation sequencing to show that three subtypes of neocortical neurons have highly distinctive epigenomic landscapes. Over 200,000 regions differ in chromatin accessibility and DNA methylation signatures characteristic of gene regulatory regions. By footprinting and motif analyses, these regions are predicted to bind distinct cohorts of neuron subtype-specific transcription factors. Neuronal epigenomes reflect both past and present gene expression, with DNA hyper-methylation at developmentally critical genes appearing as a novel epigenomic signature in mature neurons. Taken together, our findings link the functional and transcriptional complexity of neurons to their underlying epigenomic diversity.

Published
2015

14. Roles of HIFs and VEGF in angiogenesis in the retina and brain

Author

Rattner, Amir, Williams, John, and Nathans, Jeremy

Subjects
Vascular endothelial growth factor -- Analysis, Vascular diseases -- Analysis, Neurons, Endothelium, Cardiovascular diseases, DNA binding proteins, Endothelial growth factors, Newborn infants, Health care industry
Abstract

Vascular development in the mammalian retina is a paradigm for CNS vascular development in general, and its study is revealing fundamental mechanisms that explain the efficacy of antiangiogenic therapies in retinal vascular disease. During development of the mammalian retina, hypoxic astrocytes are hypothesized to secrete VEGF, which attracts growing endothelial cells as they migrate radially from the optic disc. However, published tests of this model using astrocyte-specific deletion of Vegf in the developing mouse retina appear to contradict this theory. Here, we report that selectively eliminating Vegf in neonatal retinal astrocytes with a Gfap-Cre line that recombines with approximately 100% efficiency had no effect on proliferation or radial migration of astrocytes, but completely blocked radial migration of endothelial cells, strongly supporting the hypoxic astrocyte model. Using additional Cre driver lines, we found evidence for essential and partially redundant actions of retina-derived (paracrine) and astrocyte-derived (autocrine) VEGF in controlling astrocyte proliferation and migration. We also extended previous studies by showing that Hif-1[alpha] in retinal neurons and Hif-2[alpha] in Muller glia play distinct roles in retinal vascular development and disease, adding to a growing body of data that point to the specialization of these 2 hypoxia-sensing transcription factors., Introduction Vascular development is a tightly orchestrated process that generates artery, vein, and capillary patterns and densities that are precisely calibrated to meet local tissue requirements. The master regulator of [...]

Published
2019
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24. A Common Haplotype in the Complement Regulatory Gene Factor H (HF1/CFH) Predisposes Individuals to Age-Related Macular Degeneration

Author

Hageman, Gregory S., Anderson, Don H., Johnson, Lincoln V., Hancox, Lisa S., Taiber, Andrew J., Hardisty, Lisa I., Hageman, Jill L., Stockman, Heather A., Borchardt, James D., Gehrs, Karen M., Silvestri, Giuliana, Russell, Stephen R., Barbazetto, Irene, Chang, Stanley, Yannuzzi, Lawrence A., Barile, Gaetano R., Merriam, John C., Smith, R. Theodore, Olsh, Adam K., Bergeron, Julie, Zernant, Jana, Merriam, Joanna E., Gold, Bert, Dean, Michael, Allikmets, Rando, and Nathans, Jeremy

Published
2005

39. Bistable UV Pigment in the Lamprey Pineal

Author

Koyanagi, Mitsumasa, Kawano, Emi, Kinugawa, Yoshimi, Oishi, Tadashi, Shichida, Yoshinori, Tamotsu, Satoshi, Terakita, Akihisa, and Nathans, Jeremy

Published
2004

44. A Strabismus Susceptibility Locus on Chromosome 7p

Author

Parikh, Vaishali, Shugart, Yin Yao, Doheny, Kimberly F., Zhang, Jie, Li, Lan, Williams, John, Hayden, David, Craig, Brian, Capo, Hilda, Chamblee, Denise, Chen, Cathy, Collins, Mary, Dankner, Stuart, Fiergang, Dean, Guyton, David, Hunter, David, Hutcheon, Marcia, Keys, Marshall, Morrison, Nancy, Munoz, Michelle, Parks, Marshall, Plotsky, David, Protzko, Eugene, Repka, Michael X., Sarubbi, Maria, Schnall, Bruce, Siatkowski, R. Michael, Traboulsi, Elias, Waeltermann, Joanne, and Nathans, Jeremy

Published
2003

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