A5024168775- Retinal Development and Disorders
- Renal and related cancers
- Developmental Biology and Gene Regulation
- Zebrafish Biomedical Research Applications
- Ocular Disorders and Treatments
- Retinal Diseases and Treatments
- Hedgehog Signaling Pathway Studies
- Neurobiology and Insect Physiology Research
- Connexins and lens biology
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Photoreceptor and optogenetics research
- Genomics and Chromatin Dynamics
- Neurogenesis and neuroplasticity mechanisms
- Prenatal Screening and Diagnostics
- Glaucoma and retinal disorders
- Retinopathy of Prematurity Studies
- Urological Disorders and Treatments
- Renal cell carcinoma treatment
- Epigenetics and DNA Methylation
- Retinoids in leukemia and cellular processes
- Congenital Ear and Nasal Anomalies
- Animal Genetics and Reproduction
- Chromosomal and Genetic Variations
- melanin and skin pigmentation
University of California, Davis
2015-2024
University of Michigan–Ann Arbor
2003-2015
Michigan United
2010
Harvard University
1990-2000
Howard Hughes Medical Institute
1994-2000
Massachusetts Eye and Ear Infirmary
2000
University of Georgia
2000
New York City Department of Health and Mental Hygiene
2000
University of Utah
1998
Brigham and Women's Hospital
1992-1994
Low-stringency hybridization with human glucocorticoid receptor (hGR) complementary DNA was used to isolate a new gene encoding predicted 107-kilodalton polypeptide. Expression studies demonstrate its ability bind aldosterone high affinity and activate transcription in response aldosterone, thus establishing identity as the mineralocorticoid (hMR). This molecule also shows for glucocorticoids stimulates glucocorticoid-responsive promoter. Together hMR hGR provide unexpected functional...
The vertebrate retina contains seven major neuronal and glial cell types in an interconnected network that collects, processes sends visual signals through the optic nerve to brain. Retinal neuron differentiation is thought require both intrinsic extrinsic factors, yet few gene products have been identified direct this process. Math5 (Atoh7) encodes a basic helix-loop-helix (bHLH) transcription factor specifically expressed by mouse retinal progenitors. highly homologous atonal, which...
ABSTRACT We have identified Math5, a mouse basic helix-loop-helix (bHLH) gene that is closely related to Drosophila atonal and Xenopus Xath5 largely restricted the developing eye. Math5 retinal expression precedes differentiation of first neurons persists within progenitor cells until after birth. To position in hierarchy development, we compared Hes1 wild-type Pax6-deficient (Sey) embryos. downregulated Sey/+ eyes abolished Sey/Sey eye rudiments, whereas bHLH upregulated similar...
The Maf-family transcription factor Nrl is a key regulator of photoreceptor differentiation in mammals. Ablation the gene mice leads to functional cones at expense rods. We show that 2.5-kb promoter segment directs expression enhanced GFP specifically rod photoreceptors and pineal gland transgenic mice. detected shortly after terminal cell division, corresponding timing genesis revealed by birthdating studies. In −/− retinas, GFP+ express S-opsin, consistent with transformation precursors...
Ribosomal protein mutations, termed Minutes, have been instrumental in studying the coordination of cell and tissue growth Drosophila. Although abundant flies, equivalent defects mammals are relatively unknown. Belly spot tail (Bst) is a semidominant mouse mutation that disrupts pigmentation, somitogenesis retinal fate determination. Here, we identify Bst as deletion within Rpl24 riboprotein gene. significantly impairs splicing ribosome biogenesis. Bst/+ cells decreased rates synthesis...
Retinal ganglion cells (RGCs) relay visual information from the eye to brain. RGCs are first cell type generated during retinal neurogenesis. Loss of function transcription factor Atoh7, expressed in multipotent early neurogenic progenitors leads a selective and essentially complete loss RGCs. Therefore, Atoh7 is considered essential for conferring competence on generate Despite importance RGC specification, we find that inhibiting apoptosis Atoh7-deficient mice by Bax only modestly reduces...
Aniridia is a panocular human eye malformation caused by heterozygous null mutations within PAX6 , paired-box transcription factor, or cytogenetic deletions of chromosome 11p13 that encompass . Chromosomal rearrangements also have been described disrupt but spare the unit in two families with aniridia. These presumably cause loss gene expression, removing positive cis regulatory elements juxtaposing negative DNA sequences. We report submicroscopic de novo aniridia are located >11 kb from...
Deletion of chromosome 11p13 in humans produces the WAGR syndrome, consisting aniridia (an absence or malformation iris), Wilms tumor (nephroblastoma), genitourinary malformations, and mental retardation. An interspecies backcross between Mus musculus/domesticus spretus was made order to map homologous chromosomal region mouse genome define an animal model this syndrome. Nine evolutionarily conserved DNA clones from proximal human 11p were localized on 2 near Small-eyes ( Sey ), a...
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...
Abstract Mouse microphthalmia transcription factor (Mitf) mutations affect the development of four cell types: melanocytes, mast cells, osteoclasts, and pigmented epithelial cells eye. The are phenotypically diverse can be arranged in an allelic series. In humans, MITF cause Waardenburg syndrome type 2A (WS2A) Tietz syndrome, autosomal dominant disorders resulting deafness hypopigmentation. Mitf mice thus represent important model system for study human disease. Here we report complete...
The vertebrate basic helix–loop–helix (bHLH) transcription factor ATOH7 (Math5) is specifically expressed in the embryonic neural retina and required for genesis of retinal ganglion cells (RGCs) optic nerves. In Atoh7 mutant mice, absence trophic factors secreted by RGCs prevents development intrinsic vasculature regression fetal blood vessels, causing persistent hyperplasia primary vitreous (PHPV). We therefore screened patients with hereditary PHPV, as well bilateral nerve aplasia (ONA) or...
Significance Vertebrate retinal ganglion cells (RGCs) transmit all visual signals from the eye to brain, are pathogenic target in glaucoma, and require Atoh7 competence factor develop multipotent progenitors. transcription is controlled by dual cis regulatory elements, including a remote shadow enhancer (SE). In humans, loss of SE causes NCRNA disease, with congenital blindness due optic nerve aplasia. We generated mouse deletion model analyzed its effects on transcription, histology,...
Abstract Summary: The eyeless inbred mouse strain ZRDCT has long served as a spontaneous model for human anophthalmia and the evolutionary reduction of eyes that occurred in some naturally blind mammals. mice have orbits but lack optic tracts hypothalamic abnormalities. Segregation data suggest small number interacting genes are responsible, including at least one major recessive locus, ey1 . Although predicted since 1940s, these loci were never identified. We mapped to chromosome 18 using...