Midkine-a Protein Localization in the Developing and Adult Retina of the Zebrafish and Its Function During Photoreceptor Regeneration

Gramage, Esther; D'Cruz, Travis S.; Taylor, Scott M.; Thummel, Ryan; Hitchcock, Peter F.

doi:10.1371/journal.pone.0121789

Cited by 28 publications

(31 citation statements)

References 70 publications

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“…Dividing cells were labeled with BrdU by housing animals in system water containing 5 mM BrdU for 24 hours (Gramage et al, 2015).…”

Section: Labeling Dividing Cellsmentioning

confidence: 99%

Inflammation and matrix metalloproteinase 9 (Mmp-9) regulate photoreceptor regeneration in adult zebrafish

Silva

Nagashima

et al. 2019

Preprint

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51Brain injury activates complex inflammatory signals in dying neurons, surviving neurons, and 52 glia. Here, we establish that inflammation regulates the regeneration of photoreceptors in the 53 zebrafish retina and determine the cellular expression and function of the inflammatory 54 protease, matrix metalloproteinase 9 (Mmp-9), during this regenerative neurogenesis. Animals 55 of either sex were used in this study. Following photoreceptor ablation, anti-inflammatory 56 treatment suppresses the number of injury-induced progenitors and regenerated 57 photoreceptors. Upon photoreceptor injury, mmp-9 is induced in Müller glia, the intrinsic retinal 58 stem cell, and Müller glia-derived photoreceptor progenitors. Deleting mmp-9 results in over 59 production of injury-induced progenitors and regenerated photoreceptors, but over time the 60 absence of Mmp-9 compromises the maturation and survival of the regenerated cones. Anti-61 inflammatory treatment in mutants rescues the defects in cone maturation and survival. These 62 data provide a link between injury-induced inflammation in the vertebrate CNS, Mmp-9 function 63 during photoreceptor regeneration and the requirement of Mmp-9 for the survival of regenerated 64 cones. 65 66 67 68 69 70 71 72 73 74 75 3 Significance Statement 76 77 The innate immune system is activated by neuronal death, and recent studies demonstrate that 78 in zebrafish neuroinflammation is required for neuronal regeneration. The roles of inflammatory 79 cytokines are being investigated, however, the function of the inflammatory protease, matrix 80 metalloprotease Mmp-9, in neuronal regeneration is unknown. We show herein that in adult 81 zebrafish retinal inflammation governs the proliferative phase of the stem cell-based 82 regeneration of rod and cone photoreceptors and determine the specific roles for Mmp-9 in 83 photoreceptor regeneration. This study provides the first mechanistic insights into the potential 84 role of Mmp-9 in retinal regeneration and serves to link neuroinflammation, stem cell-based 85 regeneration of photoreceptors and human photoreceptor disease. 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 2013; Zhao et al., 2014). Following a photolytic lesion, dying photoreceptors secrete Tnf-a, to 129 which Müller glia respond by partial dedifferentiation, synthesis of Tnf-a and entry into the cell 130 cycle (Nelson et al., 2013). Mechanical lesions induce the expression of leptin and Il-6 family 131 cytokines in Müller glia and Müller glia-derived progenitors and is required for injury-induced 132 proliferation (Zhao et al., 2014).133 Matrix metalloproteinase 9 (Mmp-9) is a secreted protease that plays a prominent role in 134 tissue development and homeostasis by acting on extracellular molecules, including adhesion 135

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“…Dividing cells were labeled with BrdU by housing animals in system water containing 5 mM BrdU for 24 hours (Gramage et al, 2015).…”

Section: Labeling Dividing Cellsmentioning

confidence: 99%

Inflammation and matrix metalloproteinase 9 (Mmp-9) regulate photoreceptor regeneration in adult zebrafish

Silva

Nagashima

et al. 2019

Preprint

Self Cite

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“…47 Ganglion cells are the first identifiable cells that exit the cell cycle at ~28-32 hpf and differentiation then spreads dorsally around to the ventral temporal retina in a wave-like manner. 48 The cells in the outer nuclear layer, the cone and rod photoreceptors, complete development by 72 hpf. 49 In this study, Zn12, Zpr1, and Zpr3 antibodies were used as markers to probe the differentiation of ganglion cells, cones, and rods, respectively.…”

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confidence: 99%

Effects of copper oxide nanoparticles on developing zebrafish embryos and larvae

Zhang¹,

He²,

Wang³

et al. 2016

IJN

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Copper oxide nanoparticles (CuO NPs) are used for a variety of purposes in a wide range of commercially available products. Some CuO NPs probably end up in the aquatic systems, thus raising concerns about aqueous exposure toxicity, and the impact of CuO NPs on liver development and neuronal differentiation remains unclear. In this study, particles were characterized using Fourier transform infrared spectra, scanning electron microscopy, and transmission electron microscopy. Zebrafish embryos were continuously exposed to CuO NPs from 4 hours postfertilization at concentrations of 50, 25, 12.5, 6.25, or 1 mg/L. The expression of gstp1 and cyp1a was examined by quantitative reverse transcription polymerase chain reaction. The expression of tumor necrosis factor alpha and superoxide dismutase 1 was examined by quantitative reverse transcription polymerase chain reaction and Western blotting. Liver development and retinal neurodifferentiation were analyzed by whole-mount in situ hybridization, hematoxylin–eosin staining, and immunohistochemistry, and a behavioral test was performed to track the movement of larvae. We show that exposure of CuO NPs at low doses has little effect on embryonic development. However, exposure to CuO NPs at concentrations of 12.5 mg/L or higher leads to abnormal phenotypes and induces an inflammatory response in a dose-dependent pattern. Moreover, exposure to CuO NPs at high doses results in an underdeveloped liver and a delay in retinal neurodifferentiation accompanied by reduced locomotor ability. Our data demonstrate that short-term exposure to CuO NPs at high doses shows hepatotoxicity and neurotoxicity in zebrafish embryos and larvae.

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“…EdU labelled cells were visualized using Click-iT Assay kit (Thermo Fisher Scientific). To label dividing cells in adults, animals were housed in the fish system water containing 5 mM BrdU and processed as described previously (Gramage et al, 2015).…”

Section: Edu and Brdu Labelingmentioning

confidence: 99%

“…(C) Immunocytochemistry for Midkine-a in embryonic (48 hpf), adult, and regenerating retinas. In unlesioned retina, Midkine-a immunoreactivity is detected in horizontal cells (arrowhead and (Gramage et al, 2015)). Photoreceptor cell death induces Midkine-a in reprogrammed Müller glia (arrows) at 1 dpl.…”

Section: Alk Inhibitor Treatmentmentioning

confidence: 99%

“…Post-mitotic neurons rapidly downregulate the expression of midkine-a. In adult zebrafish, retinal injury rapidly induces the expression of midkine-a in Müller glia and Müller glia-derived progenitors (Calinescu et al, 2009a;Gramage et al, 2014Gramage et al, , 2015. Induction of midkine-a expression following injury has been reported for a variety of zebrafish tissues with the capacity to regenerate (Lien et al, 2006;Ochiai et al, 2004), suggesting that Midkine may universally regulate aspects of tissue regeneration.…”

Section: Introductionmentioning

confidence: 99%

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Midkine-a is required for cell cycle progression of Müller glia during neuronal regeneration

Nagashima

D'Cruz

Hesse

et al. 2019

Preprint

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In zebrafish, Müller glia function as intrinsic retinal stem cells that can regenerate ablated neurons. Understanding the mechanisms governing neuronal stem cells may provide clues to regenerate neurons in mammals. We report that in Müller glia the cytokine/growth factor, Midkine-a, functions as a core autocrine regulator of the cell cycle. Utilizing midkine-a mutants, we determined that Midkine-a regulates elements of an Id2a-retinoblastoma network in reprogrammed Müller glia that controls the expression of cell cycle genes and is required for transition from G1 to S phases of the cell cycle. In mutants, Müller glia that fail to divide undergo reactive gliosis, a pathological hallmark of Müller glia in mammals. Finally, we show that activation of the Midkine-a receptor, ALK, is required for Müller glia proliferation. These data provide mechanistic insights into Müller glia stem cells in the vertebrate retina and suggest avenues for eliciting neuronal regeneration in mammals.

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Midkine-a Protein Localization in the Developing and Adult Retina of the Zebrafish and Its Function During Photoreceptor Regeneration

Cited by 28 publications

References 70 publications

Inflammation and matrix metalloproteinase 9 (Mmp-9) regulate photoreceptor regeneration in adult zebrafish

Inflammation and matrix metalloproteinase 9 (Mmp-9) regulate photoreceptor regeneration in adult zebrafish

Effects of copper oxide nanoparticles on developing zebrafish embryos and larvae

Midkine-a is required for cell cycle progression of Müller glia during neuronal regeneration

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