Autophagy is required for zebrafish caudal fin regeneration

Varga, Máté; Sass, Miklós; Papp, Diána; Takács‐Vellai, Krisztina; Kobolák, Julianna; Dinnyés, András; Klionsky, Daniel J.; Vellai, Tibor

doi:10.1038/cdd.2013.175

Cited by 72 publications

(69 citation statements)

References 52 publications

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“…The transcript encoding the Fat family protein fat2 is also up-regulated, consistent with the possible involvement of Fat signaling in regeneration. Other up-regulated genes suggest less characterized pathways that could affect neuromast recovery; atg2bl, for example, is a putative mediator of autophagy, a process only recently implicated in stem-cell maintenance and regeneration (60).…”

Section: Discussionmentioning

confidence: 99%

Dynamic gene expression by putative hair-cell progenitors during regeneration in the zebrafish lateral line

Steiner

Kim

Cabot

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

107

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Hearing loss is most commonly caused by the destruction of mechanosensory hair cells in the ear. This condition is usually permanent: Despite the presence of putative hair-cell progenitors in the cochlea, hair cells are not naturally replenished in adult mammals. Unlike those of the mammalian ear, the progenitor cells of nonmammalian vertebrates can regenerate hair cells throughout life. The basis of this difference remains largely unexplored but may lie in molecular dissimilarities that affect how progenitors respond to hair-cell death. To approach this issue, we analyzed gene expression in hair-cell progenitors of the lateral-line system. We developed a transgenic line of zebrafish that expresses a red fluorescent protein in the presumptive hair-cell progenitors known as mantle cells. Fluorescence-activated cell sorting from the skins of transgenic larvae, followed by microarray-based expression analysis, revealed a constellation of transcripts that are specifically enriched in these cells. Gene expression analysis after hair-cell ablation uncovered a cohort of genes that are differentially regulated early in regeneration, suggesting possible roles in the response of progenitors to hair-cell death. These results provide a resource for studying hair-cell regeneration and the biology of sensory progenitor cells.alkaline phosphatase | auditory | neuromast | supporting cell

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Section: Discussionmentioning

confidence: 99%

Dynamic gene expression by putative hair-cell progenitors during regeneration in the zebrafish lateral line

Steiner

Kim

Cabot

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

107

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“…5A to D). 45,46 The addition of AUTEN-67 at 50 mM to the samples led to a moderate intensification in Gfp fluorescence, relative to untreated control fish samples (for quantifying Gfp intensity, see the corresponding figure legend). The number of Gfp-positive spots was higher in treated samples (Figs.…”

Section: Auten-67 Increases Autophagy In Zebrafish and Micementioning

confidence: 99%

AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects

Papp¹,

Kovács

Billes

et al. 2016

Autophagy

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Autophagy is a major molecular mechanism that eliminates cellular damage in eukaryotic organisms. Basal levels of autophagy are required for maintaining cellular homeostasis and functioning. Defects in the autophagic process are implicated in the development of various age-dependent pathologies including cancer and neurodegenerative diseases, as well as in accelerated aging. Genetic activation of autophagy has been shown to retard the accumulation of damaged cytoplasmic constituents, delay the incidence of age-dependent diseases, and extend life span in genetic models. This implies that autophagy serves as a therapeutic target in treating such pathologies. Although several autophagy-inducing chemical agents have been identified, the majority of them operate upstream of the core autophagic process, thereby exerting undesired side effects. Here, we screened a small-molecule library for specific inhibitors of MTMR14, a myotubularin-related phosphatase antagonizing the formation of autophagic membrane structures, and isolated AUTEN-67 (autophagy enhancer-67) that significantly increases autophagic flux in cell lines and in vivo models. AUTEN-67 promotes longevity and protects neurons from undergoing stressinduced cell death. It also restores nesting behavior in a murine model of Alzheimer disease, without apparent side effects. Thus, AUTEN-67 is a potent drug candidate for treating autophagy-related diseases.

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“…Additionally, low function of Dicer, a key component of the miRNA synthesis machinery, showed negative effects on the fin regeneration [38]. Additional study provided evidences that upregulation of autophagy in the regeneration zone was required for the zebrafish caudal fin regeneration through preventing cells from undergoing apoptosis [41]. Calcineurin-mediated mechanism was important in the regulation of coordinated outgrowth of zebrafish regenerating fins [42].…”

Section: Fin Regenerationmentioning

confidence: 96%

Using zebrafish as the model organism to understand organ regeneration

Shi

Fang

et al. 2015

Sci. China Life Sci.

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The limited regenerative capacity of several organs, such as central nervous system (CNS), heart and limb in mammals makes related major diseases quite difficult to recover. Therefore, dissection of the cellular and molecular mechanisms underlying organ regeneration is of great scientific and clinical interests. Tremendous progression has already been made after extensive investigations using several model organisms for decades. Unfortunately, distance to the final achievement of the goal still remains. Recently, zebrafish became a popular model organism for the deep understanding of regeneration based on its powerful regenerative capacity, in particular the organs that are limitedly regenerated in mammals. Additionally, zebrafish are endowed with other advantages good for the study of organ regeneration. This review summarizes the recent progress in the study of zebrafish organ regeneration, in particular regeneration of fin, heart, CNS, and liver as the representatives. We also discuss reasons of the reduced regenerative capacity in higher vertebrate, the roles of inflammation during regeneration, and the difference between organogenesis and regeneration. organ regeneration, zebrafish, fin, heart, liver, CNS Citation:Shi WC, Fang ZB, Li L, Luo LF. Using zebrafish as the model organism to understand organ regeneration.

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Autophagy is required for zebrafish caudal fin regeneration

Cited by 72 publications

References 52 publications

Dynamic gene expression by putative hair-cell progenitors during regeneration in the zebrafish lateral line

Dynamic gene expression by putative hair-cell progenitors during regeneration in the zebrafish lateral line

AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects

Using zebrafish as the model organism to understand organ regeneration

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