A5069325928- Retinal Development and Disorders
- Developmental Biology and Gene Regulation
- Connexins and lens biology
- Zebrafish Biomedical Research Applications
- Neurogenesis and neuroplasticity mechanisms
- Corneal Surgery and Treatments
- Neurobiology and Insect Physiology Research
- Ocular Disorders and Treatments
- Photoreceptor and optogenetics research
- Ocular Oncology and Treatments
- MicroRNA in disease regulation
- Subterranean biodiversity and taxonomy
- Axon Guidance and Neuronal Signaling
- Renal and related cancers
- Photochromic and Fluorescence Chemistry
- Ubiquitin and proteasome pathways
- Glaucoma and retinal disorders
- Pluripotent Stem Cells Research
- Advanced Fluorescence Microscopy Techniques
- Retinopathy of Prematurity Studies
- Retinal Diseases and Treatments
- Hippo pathway signaling and YAP/TAZ
- Protist diversity and phylogeny
- Connective Tissue Growth Factor Research
- Hedgehog Signaling Pathway Studies
University of California, Davis
2014-2023
Cincinnati Children's Hospital Medical Center
2007-2018
University of California, San Francisco
2016
University of Cincinnati Medical Center
2006-2013
University of Cincinnati
2004-2011
Hospital Research Foundation
2010
The Royal Children's Hospital Foundation
2010
Northwestern University
2001-2006
Children’s Institute
2006
University of Michigan–Ann Arbor
2001-2003
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...
Vertebrate retinal progenitor cells (RPCs) are pluripotent, but pass through competence states that progressively restrict their developmental potential (Cepko et al., 1996; Livesey and Cepko, 2001; Cayouette 2006). In the rodent eye, seven cell classes differentiate in overlapping waves, with RGCs, cone photoreceptors, horizontals, amacrines forming predominantly before birth, rod bipolars, Müller glia differentiating postnatally. Both intrinsic extrinsic factors regulate each type (for...
Abstract Activation of the bHLH factor Math5 ( Atoh7 ) is an initiating event for mammalian retinal neurogenesis, as it critically required ganglion cell formation. However, cis‐regulatory elements and trans‐acting factors that control expression are largely unknown. Using a combination transgenic mice bioinformatics, we identified phylogenetically conserved regulatory element to activate transcription during early neurogenesis. This drives in vivo, cross‐species assay. Previously, Pax6 was...
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 Despite ongoing interest into the architecture, biochemistry, and physiology of visual systems xiphosuran Limulus polyphemus , their ontogenetic aspects have received little attention. Thus, we explored development lateral eyes associated neuropils in late embryos larvae these animals. The first external evidence was appearance white pigment spots—guanophores with rudimentary photoreceptors—on dorsolateral side embryos, suggesting that can perceive light. brown emerges during last...
Notch signaling regulates basic helix-loop-helix (bHLH) factors as an evolutionarily conserved module, but the tissue-specific mechanisms are incompletely elucidated. In mouse retina, bHLH genes Atoh7 and Neurog2 have distinct functions, with regulating retinal competence required for progression of neurogenesis. These transcription extensively co-expressed, suggesting similar regulation. We directly compared regulation at earliest stages neurogenesis in a broad spectrum pathway mutants....
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...
The bHLH transcription factor Hes1 is a key downstream effector for the Notch signaling pathway. During embryogenesis neural progenitors express low levels of in an oscillating pattern, whereas glial brain boundary regions (e.g., isthmus) have high, sustained that suppress neuronal fates. Here, we show embryonic mouse retina, optic nerve head and stalk high Hes1, with ONH constituting between retina cells ultimately line stalk. Using two Cre drivers distinct spatiotemporal expression...
To determine how the absence of retinal ganglion cells (RGCs) in Math5 (Atoh7) mutant mice affects circadian behavior and function.The wheel-running wild-type was measured under various light-dark cycle conditions. evaluate input to suprachiasmatic nuclei (SCN) anatomically, retinohypothalamic tracts were labeled vivo. assess changes function, corneal flash electroretinograms (ERGs) from compared dark- light-adapted Alterations neuron populations evaluated quantitatively with...
ABSTRACT The regulatory gene hairy is expressed and required during early embryogenesis to control segmentation expression properly larval pupal development the pattern of certain adult sensory structures. We have found protein be transiently two stages eye imaginai disc development, including all cells immediately anterior morphogenetic furrow that traverses developing disc, again in presumptive R7 photoreceptor ommatidia. This conserved a significantly diverged Drosophila species. show...
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...
Abstract Pax6 regulates eye development in many animals. In addition, activates atonal transcription factors both invertebrate and vertebrate eyes. Here, we investigate the roles of during embryonic Limulus polyphemus rudimentary lateral, medial ventral eyes, initiation lateral ommatidial ocelli formation. is particular interest because these animals hold a unique position arthropod phylogeny possess multiple types. Furthermore, molecular underpinnings have yet to be investigated...