Wnt signaling regulates proliferation and differentiation of radial glia in regenerative processes after stab injury in the optic tectum of adult zebrafish

Glia ◽  
2018 ◽  
Vol 66 (7) ◽  
pp. 1382-1394 ◽  
Author(s):  
Yuki Shimizu ◽  
Yuto Ueda ◽  
Toshio Ohshima
Keyword(s):  
Wnt Signaling ◽  
Optic Tectum ◽  
Radial Glia ◽  
Adult Zebrafish ◽  
Regenerative Processes ◽  
Stab Injury ◽  
Proliferation And Differentiation

scholarly journals Transcriptome Analyses Reveal IL6/Stat3 Signaling Involvement in Radial Glia Proliferation After Stab Wound Injury in the Adult Zebrafish Optic Tectum

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuki Shimizu ◽  
Mariko Kiyooka ◽  
Toshio Ohshima
Keyword(s):  
Optic Tectum ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Radial Glia ◽  
Stab Wound ◽  
Cytokine Signaling ◽  
Adult Zebrafish ◽  
Stat3 Signaling ◽  
Proliferation And Differentiation ◽  
Zebrafish Optic Tectum

Adult zebrafish have many neurogenic niches and a high capacity for central nervous system regeneration compared to mammals, including humans and rodents. The majority of radial glia (RG) in the zebrafish optic tectum are quiescent under physiological conditions; however, stab wound injury induces their proliferation and differentiation into newborn neurons. Although previous studies have functionally analyzed the molecular mechanisms of RG proliferation and differentiation and have performed single-cell transcriptomic analyses around the peak of RG proliferation, the cellular response and changes in global gene expression during the early stages of tectum regeneration remain poorly understood. In this study, we performed histological analyses which revealed an increase in isolectin B4+ macrophages prior to the induction of RG proliferation. Moreover, transcriptome and pathway analyses based on differentially expressed genes identified various enriched pathways, including apoptosis, the innate immune system, cell proliferation, cytokine signaling, p53 signaling, and IL6/Jak-Stat signaling. In particular, we found that Stat3 inhibition suppressed RG proliferation after stab wound injury and that IL6 administration into cerebroventricular fluid activates RG proliferation without causing injury. Together, the findings of these transcriptomic and functional analyses reveal that IL6/Stat3 signaling is an initial trigger of RG activation during optic tectum regeneration.

Involvement of sonic hedgehog and notch signaling in regenerative neurogenesis in adult zebrafish optic tectum after stab injury

2018 ◽  
Vol 526 (15) ◽  
pp. 2360-2372 ◽  
Author(s):  
Yuto Ueda ◽  
Yuki Shimizu ◽  
Nobuyuki Shimizu ◽  
Tohru Ishitani ◽  
Toshio Ohshima
Keyword(s):  
Notch Signaling ◽  
Sonic Hedgehog ◽  
Optic Tectum ◽  
Adult Zebrafish ◽  
Stab Injury ◽  
Zebrafish Optic Tectum

scholarly journals Critical Effects on Akt Signaling in Adult Zebrafish Brain Following Alterations in Light Exposure

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 637
Author(s):  
Nicholas S. Moore ◽  
Robert A. Mans ◽  
Mackenzee K. McCauley ◽  
Colton S. Allgood ◽  
Keri A. Barksdale
Keyword(s):  
Optic Tectum ◽  
Visual Processing ◽  
Environmental Enrichment ◽  
Glycogen Synthase ◽  
Light Exposure ◽  
Hsp70 Expression ◽  
Light Cycle ◽  
Adult Zebrafish ◽  
Sleep State ◽  
Zebrafish Brain

Evidence from human and animal studies indicate that disrupted light cycles leads to alterations of the sleep state, poor cognition, and the risk of developing neuroinflammatory and generalized health disorders. Zebrafish exhibit a diurnal circadian rhythm and are an increasingly popular model in studies of neurophysiology and neuropathophysiology. Here, we investigate the effect of alterations in light cycle on the adult zebrafish brain: we measured the effect of altered, unpredictable light exposure in adult zebrafish telencephalon, homologous to mammalian hippocampus, and the optic tectum, a significant visual processing center with extensive telencephalon connections. The expression of heat shock protein-70 (HSP70), an important cell stress mediator, was significantly decreased in optic tectum of adult zebrafish brain following four days of altered light exposure. Further, pSer473-Akt (protein kinase B) was significantly reduced in telencephalon following light cycle alteration, and pSer9-GSK3β (glycogen synthase kinase-3β) was significantly reduced in both the telencephalon and optic tectum of light-altered fish. Animals exposed to five minutes of environmental enrichment showed significant increase in pSer473Akt, which was significantly attenuated by four days of altered light exposure. These data show for the first time that unpredictable light exposure alters HSP70 expression and dysregulates Akt-GSK3β signaling in the adult zebrafish brain.

scholarly journals Notch-Wnt signal crosstalk regulates proliferation and differentiation of osteoprogenitor cells during intramembranous bone healing

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
S. Lee ◽  
L. H. Remark ◽  
A. M. Josephson ◽  
K. Leclerc ◽  
E. Muiños Lopez ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Notch Signaling ◽  
Bone Regeneration ◽  
Bone Healing ◽  
Canonical Wnt Signaling ◽  
Osteoprogenitor Cells ◽  
Intramembranous Bone ◽  
Proliferation And Differentiation ◽  
Canonical Wnt ◽  
Wnt Signal

AbstractAdult bone regeneration is orchestrated by the precise actions of osteoprogenitor cells (OPCs). However, the mechanisms by which OPC proliferation and differentiation are linked and thereby regulated are yet to be defined. Here, we present evidence that during intramembranous bone formation OPC proliferation is controlled by Notch signaling, while differentiation is initiated by activation of canonical Wnt signaling. The temporospatial separation of Notch and Wnt signal activation during the early stages of bone regeneration suggests crosstalk between the two pathways. In vitro and in vivo manipulation of the two essential pathways demonstrate that Wnt activation leads to initiation of osteogenic differentiation and at the same time inhibits Notch signaling, which results in termination of the proliferative phase. Here, we establish canonical Wnt signaling as a key regulator that facilitates the crosstalk between OPC proliferation and differentiation during intramembranous, primary bone healing.

scholarly journals Adaptation-induced modification of motion selectivity tuning in visual tectal neurons of adult zebrafish

2015 ◽  
Vol 114 (5) ◽  
pp. 2893-2902 ◽  
Author(s):  
Vanessa Hollmann ◽  
Valerie Lucks ◽  
Rafael Kurtz ◽  
Jacob Engelmann
Keyword(s):  
Optic Tectum ◽  
Brain Area ◽  
Direction Selectivity ◽  
Adult Brain ◽  
Orientation Tuning ◽  
Adult Zebrafish ◽  
Short Term ◽  
Short Term Plasticity ◽  
The Difference ◽  
Tectal Neurons

In the developing brain, training-induced emergence of direction selectivity and plasticity of orientation tuning appear to be widespread phenomena. These are found in the visual pathway across different classes of vertebrates. Moreover, short-term plasticity of orientation tuning in the adult brain has been demonstrated in several species of mammals. However, it is unclear whether neuronal orientation and direction selectivity in nonmammalian species remains modifiable through short-term plasticity in the fully developed brain. To address this question, we analyzed motion tuning of neurons in the optic tectum of adult zebrafish by calcium imaging. In total, orientation and direction selectivity was enhanced by adaptation, responses of previously orientation-selective neurons were sharpened, and even adaptation-induced emergence of selectivity in previously nonselective neurons was observed in some cases. The different observed effects are mainly based on the relative distance between the previously preferred and the adaptation direction. In those neurons in which a shift of the preferred orientation or direction was induced by adaptation, repulsive shifts (i.e., away from the adapter) were more prevalent than attractive shifts. A further novel finding for visually induced adaptation that emerged from our study was that repulsive and attractive shifts can occur within one brain area, even with uniform stimuli. The type of shift being induced also depends on the difference between the adapting and the initially preferred stimulus direction. Our data indicate that, even within the fully developed optic tectum, short-term plasticity might have an important role in adjusting neuronal tuning functions to current stimulus conditions.

scholarly journals Differential Regenerative Capacity of the Optic Tectum of Adult Medaka and Zebrafish

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuki Shimizu ◽  
Takashi Kawasaki
Keyword(s):  
Optic Tectum ◽  
Radial Glia ◽  
Stab Wound ◽  
Brain Structures ◽  
Post Injury ◽  
Regenerative Capacity ◽  
Injured Area ◽  
Brain Regeneration ◽  
The Central Nervous System ◽  
Regenerative Ability

Zebrafish have superior regenerative capacity in the central nervous system (CNS) compared to mammals. In contrast, medaka were shown to have low regenerative capacity in the adult heart and larval retina, despite the well-documented high tissue regenerative ability of teleosts. Nevertheless, medaka and zebrafish share similar brain structures and biological features to those of mammals. Hence, this study aimed to compare the neural stem cell (NSC) responses and regenerative capacity in the optic tectum of adult medaka and zebrafish after stab wound injury. Limited neuronal differentiation was observed in the injured medaka, though the proliferation of radial glia (RG) was induced in response to tectum injury. Moreover, the expression of the pro-regenerative transcriptional factors ascl1a and oct4 was not enhanced in the injured medaka, unlike in zebrafish, whereas expression of sox2 and stat3 was upregulated in both fish models. Of note, glial scar-like structures composed of GFAP+ radial fibers were observed in the injured area of medaka at 14 days post injury (dpi). Altogether, these findings suggest that the adult medaka brain has low regenerative capacity with limited neuronal generation and scar formation. Hence, medaka represent an attractive model for investigating and evaluating critical factors for brain regeneration.

scholarly journals Induction of Oxidative Stress and Apoptosis in the Injured Brain: Potential Relevance to Brain Regeneration in Zebrafish.

2021 ◽  
Author(s):  
Surendra Kumar Anand ◽  
Manas Ranjan Sahu ◽  
Amal Chandra Mondal
Keyword(s):  
Oxidative Stress ◽  
Mrna Levels ◽  
Adult Zebrafish ◽  
Zebrafish Model ◽  
Stab Injury ◽  
Zebrafish Brain ◽  
Protein Levels ◽  
Injured Brain ◽  
Brain Regeneration ◽  
The Impact

Abstract In the recent years, zebrafish, owing to its tremendous adult neurogenic capacity, has emerged as a useful vertebrate model to study brain regeneration. Recent findings suggest a significant role of the BDNF/TrkB signaling as a mediator of brain regeneration following a stab injury in the adult zebrafish brain. Since BDNF has been implicated in a plethora of physiological processes, we hypothesized that these processes are affected in the injured zebrafish brain. In this small study, we examined the indicators of oxidative stress and of apoptosis using biochemical assays, RT-PCR and IHC to reflect upon the impact of stab injury on oxidative stress levels and apoptosis in the injured adult zebafish brain. Our results indicate induction of oxidative stress in the injured adult zebrafish brain. Also, apoptosis was induced in the injured brain as indicated by increased protein levels of cleaved caspase3 as well as enhanced mRNA levels of both pro-apoptotic and anti-apoptotic genes. This knowledge contributes to the overall understanding of adult neurogenesis in the zebrafish model and raises new questions pertaining to the compensatory physiological mechanisms in response to traumatic brain injury in the adult zebrafish brain.

scholarly journals Neddylation is critical to cortical development by regulating Wnt/β-catenin signaling

2020 ◽  
Vol 117 (42) ◽  
pp. 26448-26459 ◽  
Author(s):  
Lei Zhang ◽  
Hongyang Jing ◽  
Haiwen Li ◽  
Wenbing Chen ◽  
Bin Luo ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Protein Modification ◽  
Radial Glia ◽  
Critical Role ◽  
Cortical Development ◽  
Nuclear Accumulation ◽  
Progressive Reduction ◽  
Intermediate Progenitors

Wnt signaling plays a critical role in production and differentiation of neurons and undergoes a progressive reduction during cortical development. However, how Wnt signaling is regulated is not well understood. Here we provide evidence for an indispensable role of neddylation, a ubiquitylation-like protein modification, in inhibiting Wnt/β-catenin signaling. We show that β-catenin is neddylated; and inhibiting β-catenin neddylation increases its nuclear accumulation and Wnt/β-catenin signaling. To test this hypothesis in vivo, we mutated Nae1, an obligative subunit of the E1 for neddylation in cortical progenitors. The mutation leads to eventual reduction in radial glia progenitors (RGPs). Consequently, the production of intermediate progenitors (IPs) and neurons is reduced, and neuron migration is impaired, resulting in disorganization of the cerebral cortex. These phenotypes are similar to those of β-catenin gain-of-function mice. Finally, suppressing β-catenin expression is able to rescue deficits of Nae1 mutant mice. Together, these observations identified a mechanism to regulate Wnt/β-catenin signaling in cortical development.

scholarly journals Calsequestrins New Calcium Store Markers of Adult Zebrafish Cerebellum and Optic Tectum

2020 ◽  
Vol 14 ◽  
Author(s):  
Sandra Furlan ◽  
Marina Campione ◽  
Marta Murgia ◽  
Simone Mosole ◽  
Francesco Argenton ◽  
...  
Keyword(s):  
Optic Tectum ◽  
Adult Zebrafish ◽  
Calcium Store
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