- Retinal Development and Disorders
- Zebrafish Biomedical Research Applications
- Neurogenesis and neuroplasticity mechanisms
- Congenital heart defects research
- Nerve injury and regeneration
- Retinoids in leukemia and cellular processes
- Proteoglycans and glycosaminoglycans research
- Neuroinflammation and Neurodegeneration Mechanisms
- Calpain Protease Function and Regulation
- Developmental Biology and Gene Regulation
- Hippo pathway signaling and YAP/TAZ
- Retinal Diseases and Treatments
- interferon and immune responses
- Cellular Mechanics and Interactions
- Advanced Fluorescence Microscopy Techniques
- Connexins and lens biology
- Physiological and biochemical adaptations
- Aquaculture Nutrition and Growth
- Kruppel-like factors research
- Heat shock proteins research
- Nitric Oxide and Endothelin Effects
- Cell death mechanisms and regulation
- Photochromic and Fluorescence Chemistry
- Bee Products Chemical Analysis
- Protein Tyrosine Phosphatases
University of Michigan
2013-2023
Michigan United
2014-2020
Kanazawa University
2006-2014
Müller glia function as retinal stem cells in adult zebrafish. In response to loss of neurons, partially dedifferentiate, re-express neuroepithelial markers and re-enter the cell cycle. We show that immunoglobulin superfamily adhesion molecule Alcama is a novel marker multipotent cells, including injury-induced glia, each glial divides asymmetrically only once produce an Alcama-negative, proliferating progenitor. The initial mitotic division involves interkinetic nuclear migration, but...
Abstract Brain injury activates complex inflammatory signals in dying neurons, surviving and glia. Here, we establish that inflammation regulates the regeneration of photoreceptors zebrafish retina determine cellular expression function protease, matrix metalloproteinase 9 (Mmp‐9), during this regenerative neurogenesis. Following photoreceptor ablation, anti‐inflammatory treatment suppresses number injury‐induced progenitors regenerated photoreceptors. Upon injury, mmp‐9 is induced Müller...
Following acute retinal damage, zebrafish possess the ability to regenerate all neuronal subtypes through Müller glia (MG) reprogramming and asymmetric cell division that produces a multipotent glia-derived progenitor (MGPC). This raises three key questions. First, do MG reprogram developmental (RPC) state? Second, what extent does regeneration recapitulate development? And finally, loss of different induce unique responses? We examined these questions by performing single-nuclear...
Cone photoreceptors in teleost fish are organized precise, crystalline arrays the epithelial plane of retina. In zebrafish, four distinct morphological/spectral cone types occupy specific, invariant positions within a regular lattice. The lattice is aligned orthogonal and parallel to circumference retinal hemisphere: it emerges as cones generated germinal zone at periphery incorporated single-cell columns into Genetic disruption transcription factor Tbx2b eliminates most subtype maximally...
In the retina of zebrafish, Müller glia have ability to reprogram into stem cells capable regenerating all classes retinal neurons and restoring visual function. Understanding cellular molecular mechanisms controlling cell properties in zebrafish may provide cues unlock regenerative potential mammalian nervous system. Midkine is a cytokine/growth factor with multiple roles neural development, tissue repair, disease. midkine-a loss-of-function mutants both sexes, initiate appropriate...
Fish retinal ganglion cells (RGCs) can regenerate their axons after optic nerve injury, whereas mammalian RGCs normally fail to do so. Interleukin 6 (IL-6)-type cytokines are involved in cell differentiation, proliferation, survival, and axon regrowth; thus, they may play a role the regeneration of zebrafish injury. In this study, we assessed expression IL-6-type found that one them, leukemia inhibitory factor (LIF), is upregulated at 3 days post-injury (dpi). We then demonstrated activation...
Nitric oxide (NO) signaling results in both neurotoxic and neuroprotective effects CNS PNS neurons, respectively, after nerve lesioning. We investigated the role of NO on optic regeneration goldfish (Carassius auratus). NADPH diaphorase staining revealed that nitric synthase (NOS) activity was up-regulated primarily retinal ganglion cells (RGCs) 5-40 days axotomy. Levels neuronal NOS (nNOS) mRNA protein also increased RGCs alone during this period. This period (5-40 days) overlapped with...
The multiplex, lattice mosaic of cone photoreceptors in the adult fish retina is a compelling example highly ordered epithelial cell pattern, with single width rows and columns cones precisely defined neighbor relationships among different types. Cellular mechanisms patterning this multiplex are not understood. Physical models can provide new insights into fundamental biological patterning. In earlier work, we developed mathematical model photoreceptor packing zebrafish retina, which...
Zebrafish have the ability to regenerate damaged cells and tissues by activating quiescent stem progenitor or reprogramming differentiated into regeneration-competent precursors. Proliferation among that will functionally restore injured is a fundamental biological process underlying regeneration. Midkine-a cytokine growth factor, whose expression strongly induced injury in variety of across range vertebrate classes. Using zebrafish loss function mutant, we evaluated regeneration caudal fin,...
Endothelial cells emerge from the atrioventricular canal to form coronary blood vessels in juvenile zebrafish hearts. We find that pdgfrb is first expressed epicardium around and later becomes localized mainly mural cells. mutant fish show severe defects cell recruitment vessel development. Single-cell RNA sequencing analyses identified pdgfrb+ as epicardium-derived (EPDCs) Mural associated with arteries also express cxcl12b smooth muscle markers. Interestingly, these remain even absence of...
Purpose: Human Crb1 is implicated in some forms of retinal degeneration, suggesting a role photoreceptor maintenance. Multiple Crumbs (Crb) polarity genes are expressed vertebrate retina, although their functional roles not well understood. To gain further insight into Crb and maintenance, we compared cell densities between wild-type Tg(RH2-2:Crb2b-sfEX/RH2-2:GFP)pt108b transgenic zebrafish, which the extracellular domain Crb2b-short form (Crb2b-sfEX) retina as secreted protein, disrupts...
The outer epithelial layer of zebrafish retinae contains a crystalline array cone photoreceptors, called the mosaic. As this mosaic grows by mitotic addition new photoreceptors at rim hemispheric retina, topological defects, "Y-Junctions", form to maintain approximately constant cell spacing. generation defects due growth on curved surface is distinct feature not seen in other well-studied biological patterns like R8 photoreceptor Drosophila compound eye. Since can provide insight into...
Abstract Brain injury activates complex inflammatory signals in dying neurons, surviving and glia. Here, we establish that inflammation regulates the regeneration of photoreceptors zebrafish retina determine cellular expression function protease, matrix metalloproteinase 9 (Mmp-9), during this regenerative neurogenesis. Following sterile photoreceptor ablation anti-inflammatory treatment suppresses both number injury-induced progenitors regenerated photoreceptors. Upon injury, mmp-9 is...
Following acute retinal damage, zebrafish possess the ability to regenerate all neuronal subtypes. This regeneration requires Müller glia (MG) reprogram and divide asymmetrically produce a multipotent glia-derived progenitor cell (MGPC). raises three key questions. First, does loss of different subtypes induce unique MG responses? Second, do developmental state? And finally, what extent recapitulate development? We examined these questions by performing single-nuclear single-cell RNA-Seq...
Summary In zebrafish, Müller glia function as intrinsic retinal stem cells that can regenerate ablated neurons. Understanding the mechanisms governing neuronal may provide clues to neurons in mammals. We report cytokine/growth factor, Midkine-a, functions a core autocrine regulator of cell cycle. Utilizing midkine-a mutants, we determined Midkine-a regulates elements an Id2a-retinoblastoma network reprogrammed controls expression cycle genes and is required for transition from G1 S phases...