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Beta cell regeneration zebrafish

David Bergemann, Laura Massoz, Jordane Bourdouxhe, Claudio A Carril Pardo, Marianne L Voz, Bernard Peers, Isabelle Manfroid
The zebrafish is a popular animal model with well-known regenerative capabilities. To study regeneration in this fish, the nitroreductase/metronidazole-mediated system is widely used for targeted ablation of various cell types. Nevertheless, we highlight here some variability in ablation efficiencies with the metronidazole prodrug that led us to search for a more efficient and reliable compound. Herein, we present nifurpirinol, another nitroaromatic antibiotic, as a more potent prodrug compared to metronidazole to trigger cell-ablation in nitroreductase expressing transgenic models...
April 17, 2018: Wound Repair and Regeneration
Shu-Bing Huang, Hou-De Zhao, Lin-Fang Wang, Meng-Fei Sun, Ying-Li Zhu, Yi-Bo Wu, Yi-Da Xu, Shi-Xiao Peng, Chun Cui, Yan-Qin Shen
Human spinal cord injury (SCI) usually causes irreversible disability beneath the injured site due to poor neural regeneration. On the contrary, zebrafish show significant regenerative ability after SCI, thus is usually worked as an animal model for studying neuroregeneration. Most of the previous SCI studies focused on the local site of SCI, the supraspinal-derived signals were rarely mentioned. Here we showed that intradiencephalon injection of histamine (HA) inhibited the locomotor recovery in adult zebrafish post-SCI...
July 29, 2017: Biochemical and Biophysical Research Communications
Tomoya Hasegawa, Christopher J Hall, Philip S Crosier, Gembu Abe, Koichi Kawakami, Akira Kudo, Atsushi Kawakami
Cellular responses to injury are crucial for complete tissue regeneration, but their underlying processes remain incompletely elucidated. We have previously reported that myeloid-defective zebrafish mutants display apoptosis of regenerative cells during fin fold regeneration. Here, we found that the apoptosis phenotype is induced by prolonged expression of interleukin 1 beta ( il1b ). Myeloid cells are considered to be the principal source of Il1b, but we show that epithelial cells express il1b in response to tissue injury and initiate the inflammatory response, and that its resolution by macrophages is necessary for survival of regenerative cells...
February 23, 2017: ELife
Christoph Tappeiner, Ellinor Maurer, Pauline Sallin, Thomas Bise, Volker Enzmann, Markus Tschopp
In contrast to the mammalian retina, the zebrafish retina exhibits the potential for lifelong retinal neurogenesis and regeneration even after severe damage. Previous studies have shown that the transforming growth factor beta (TGFβ) signaling pathway is activated during the regeneration of different tissues in the zebrafish and is needed for regeneration in the heart and the fin. In this study, we have investigated the role of the TGFβ pathway in the N-methyl-N-nitrosourea (MNU)-induced chemical model of rod photoreceptor de- and regeneration in adult zebrafish...
2016: PloS One
Wuhong Pei, Sunny C Huang, Lisha Xu, Kade Pettie, María Laura Ceci, Mario Sánchez, Miguel L Allende, Shawn M Burgess
BACKGROUND: We are using genetics to identify genes specifically involved in hearing regeneration. In a large-scale genetic screening, we identified mgat5a, a gene in the N-glycosylation biosynthesis pathway whose activity negatively impacts hair cell regeneration. METHODS: We used a combination of mutant analysis in zebrafish and a hair cell regeneration assay to phenotype the loss of Mgat5a activity in zebrafish. We used pharmacological inhibition of N-glycosylation by swansonine...
2016: Cell Regeneration
Jie Yang, Junnai Wang, Zhen Zeng, Long Qiao, Liang Zhuang, Lijun Jiang, Juncheng Wei, Quanfu Ma, Mingfu Wu, Shuangmei Ye, Qinglei Gao, Ding Ma, Xiaoyuan Huang
Transforming growth factor-beta (TGF-beta) regulates cellular functions and plays key roles in development and carcinogenesis. Smad4 is the central intracellular mediator of TGF-beta signaling and plays crucial roles in tissue regeneration, cell differentiation, embryonic development, regulation of the immune system and tumor progression. To clarify the role of smad4 in development, we examined both the pattern of smad4 expression in zebrafish embryos and the effect of smad4 suppression on embryonic development using smad4-specific antisense morpholino-oligonucleotides...
October 2016: Differentiation; Research in Biological Diversity
Lihua Ye, Morgan A Robertson, Teresa L Mastracci, Ryan M Anderson
As one of the key nutrient sensors, insulin signaling plays an important role in integrating environmental energy cues with organism growth. In adult organisms, relative insufficiency of insulin signaling induces compensatory expansion of insulin-secreting pancreatic beta (β) cells. However, little is known about how insulin signaling feedback might influence neogenesis of β cells during embryonic development. Using genetic approaches and a unique cell transplantation system in developing zebrafish, we have uncovered a novel role for insulin signaling in the negative regulation of pancreatic progenitor cell differentiation...
January 15, 2016: Developmental Biology
Aurélie P Ghaye, David Bergemann, Estefania Tarifeño-Saldivia, Lydie C Flasse, Virginie Von Berg, Bernard Peers, Marianne L Voz, Isabelle Manfroid
BACKGROUND: In contrast to mammals, the zebrafish has the remarkable capacity to regenerate its pancreatic beta cells very efficiently. Understanding the mechanisms of regeneration in the zebrafish and the differences with mammals will be fundamental to discovering molecules able to stimulate the regeneration process in mammals. To identify the pancreatic cells able to give rise to new beta cells in the zebrafish, we generated new transgenic lines allowing the tracing of multipotent pancreatic progenitors and endocrine precursors...
2015: BMC Biology
Chen-Hui Chen, Alexander F Merriman, Jeremiah Savage, Jason Willer, Taylor Wahlig, Nicholas Katsanis, Viravuth P Yin, Kenneth D Poss
The first critical stage in salamander or teleost appendage regeneration is creation of a specialized epidermis that instructs growth from underlying stump tissue. Here, we performed a forward genetic screen for mutations that impair this process in amputated zebrafish fins. Positional cloning and complementation assays identified a temperature-sensitive allele of the ECM component laminin beta 1a (lamb1a) that blocks fin regeneration. lamb1a, but not its paralog lamb1b, is sharply induced in a subset of epithelial cells after fin amputation, where it is required to establish and maintain a polarized basal epithelial cell layer...
August 2015: PLoS Genetics
Lihua Ye, Morgan A Robertson, Daniel Hesselson, Didier Y R Stainier, Ryan M Anderson
The interconversion of cell lineages via transdifferentiation is an adaptive mode of tissue regeneration and an appealing therapeutic target. However, its clinical exploitation is contingent upon the discovery of contextual regulators of cell fate acquisition and maintenance. In murine models of diabetes, glucagon-secreting alpha cells transdifferentiate into insulin-secreting beta cells following targeted beta cell depletion, regenerating the form and function of the pancreatic islet. However, the molecular triggers of this mode of regeneration are unknown...
April 15, 2015: Development
Takeru Kashiwada, Shigetomo Fukuhara, Kenta Terai, Toru Tanaka, Yuki Wakayama, Koji Ando, Hiroyuki Nakajima, Hajime Fukui, Shinya Yuge, Yoshinobu Saito, Akihiko Gemma, Naoki Mochizuki
β-catenin regulates the transcription of genes involved in diverse biological processes, including embryogenesis, tissue homeostasis and regeneration. Endothelial cell (EC)-specific gene-targeting analyses in mice have revealed that β-catenin is required for vascular development. However, the precise function of β-catenin-mediated gene regulation in vascular development is not well understood, since β-catenin regulates not only gene expression but also the formation of cell-cell junctions. To address this question, we have developed a novel transgenic zebrafish line that allows the visualization of β-catenin transcriptional activity specifically in ECs and discovered that β-catenin-dependent transcription is central to the bone morphogenetic protein (Bmp)-mediated formation of venous vessels...
February 1, 2015: Development
Mara E Pitulescu, Ralf H Adams
Blood vessels and the lymphatic vasculature are extensive tubular networks formed by endothelial cells that have several indispensable functions in the developing and adult organism. During growth and tissue regeneration but also in many pathological settings, these vascular networks expand, which is critically controlled by the receptor EphB4 and the ligand ephrin-B2. An increasing body of evidence links Eph/ephrin molecules to the function of other receptor tyrosine kinases and cell surface receptors. In the endothelium, ephrin-B2 is required for clathrin-dependent internalization and full signaling activity of VEGFR2, the main receptor for vascular endothelial growth factor...
2014: Cell Adhesion & Migration
Jin Wan, Xiao-Feng Zhao, Anne Vojtek, Daniel Goldman
Müller glia (MG) in the zebrafish retina respond to retinal injury by generating multipotent progenitors for retinal repair. Here, we show that Insulin, Igf-1, and fibroblast growth factor (FGF) signaling components are necessary for retina regeneration. Interestingly, these factors synergize with each other and with heparin-binding EGF-like growth factor (HB-EGF) and cytokines to stimulate MG to generate multipotent progenitors in the uninjured retina. These factors act by stimulating a core set of signaling cascades (Mapk/Erk, phosphatidylinositol 3-kinase [PI3K], β-catenin, and pStat3) that are also shared with retinal injury and exhibit a remarkable amount of crosstalk...
October 9, 2014: Cell Reports
Tseng-Ting Kao, Chia-Yi Chu, Gang-Hui Lee, Tsun-Hsien Hsiao, Nai-Wei Cheng, Nan-Shan Chang, Bing-Hung Chen, Tzu-Fun Fu
Folate is a nutrient essential for the development, function and regeneration of nervous systems. Folate deficiency has been linked to many neurological disorders including neural tube defects in fetus and Alzheimer's diseases in the elderly. However, the etiology underlying these folate deficiency-associated diseases is not completely understood. In this study, zebrafish transgenic lines with timing and duration-controllable folate deficiency were developed by ectopically overexpressing a recombinant EGFP-γ-glutamyl hydrolase (γGH)...
November 2014: Neurobiology of Disease
Naoki Tsuji, Nikolay Ninov, Mina Delawary, Sahar Osman, Alex S Roh, Philipp Gut, Didier Y R Stainier
Inducing beta-cell mass expansion in diabetic patients with the aim to restore glucose homeostasis is a promising therapeutic strategy. Although several in vitro studies have been carried out to identify modulators of beta-cell mass expansion, restoring endogenous beta-cell mass in vivo has yet to be achieved. To identify potential stimulators of beta-cell replication in vivo, we established transgenic zebrafish lines that monitor and allow the quantification of cell proliferation by using the fluorescent ubiquitylation-based cell cycle indicator (FUCCI) technology...
2014: PloS One
Linjia Jiang, Andres Romero-Carvajal, Jeff S Haug, Christopher W Seidel, Tatjana Piotrowski
Deafness caused by the terminal loss of inner ear hair cells is one of the most common sensory diseases. However, nonmammalian animals (e.g., birds, amphibians, and fish) regenerate damaged hair cells. To understand better the reasons underpinning such disparities in regeneration among vertebrates, we set out to define at high resolution the changes in gene expression associated with the regeneration of hair cells in the zebrafish lateral line. We performed RNA-Seq analyses on regenerating support cells purified by FACS...
April 8, 2014: Proceedings of the National Academy of Sciences of the United States of America
Lucie Tumova, Antonio R Pombinho, Martina Vojtechova, Jitka Stancikova, Dietmar Gradl, Michaela Krausova, Eva Sloncova, Monika Horazna, Vitezslav Kriz, Olga Machonova, Jindrich Jindrich, Zbynek Zdrahal, Petr Bartunek, Vladimir Korinek
The Wnt signaling pathway is required during embryonic development and for the maintenance of homeostasis in adult tissues. However, aberrant activation of the pathway is implicated in a number of human disorders, including cancer of the gastrointestinal tract, breast, liver, melanoma, and hematologic malignancies. In this study, we identified monensin, a polyether ionophore antibiotic, as a potent inhibitor of Wnt signaling. The inhibitory effect of monensin on the Wnt/β-catenin signaling cascade was observed in mammalian cells stimulated with Wnt ligands, glycogen synthase kinase-3 inhibitors, and in cells transfected with β-catenin expression constructs...
April 2014: Molecular Cancer Therapeutics
Scott Stewart, Alan W Gomez, Benjamin E Armstrong, Astra Henner, Kryn Stankunas
Zebrafish fully regenerate lost bone, including after fin amputation, through a process mediated by dedifferentiated, lineage-restricted osteoblasts. Mechanisms controlling the osteoblast regenerative program from its initiation through reossification are poorly understood. We show that fin amputation induces a Wnt/β-catenin-dependent epithelial to mesenchymal transformation (EMT) of osteoblasts in order to generate proliferative Runx2(+) preosteoblasts. Localized Wnt/β-catenin signaling maintains this progenitor population toward the distal tip of the regenerative blastema...
February 13, 2014: Cell Reports
Bonnie E Jacques, William H Montgomery, Phillip M Uribe, Andrew Yatteau, James D Asuncion, Genesis Resendiz, Jonathan I Matsui, Alain Dabdoub
Canonical Wnt/β-catenin signaling has been implicated in multiple developmental events including the regulation of proliferation, cell fate, and differentiation. In the inner ear, Wnt/β-catenin signaling is required from the earliest stages of otic placode specification through the formation of the mature cochlea. Within the avian inner ear, the basilar papilla (BP), many Wnt pathway components are expressed throughout development. Here, using reporter constructs for Wnt/β-catenin signaling, we show that this pathway is active throughout the BP (E6-E14) in both hair cells (HCs) and supporting cells...
April 2014: Developmental Neurobiology
Jenny R Lenkowski, Zhao Qin, Christopher J Sifuentes, Ryan Thummel, Celina M Soto, Cecilia B Moens, Pamela A Raymond
Müller glia are the resident radial glia in the vertebrate retina. The response of mammalian Müller glia to retinal damage often results in a glial scar and no functional replacement of lost neurons. Adult zebrafish Müller glia, in contrast, are considered tissue-specific stem cells that can self-renew and generate neurogenic progenitors to regenerate all retinal neurons after damage. Here, we demonstrate that regulation of TGFβ signaling by the corepressors Tgif1 and Six3b is critical for the proliferative response to photoreceptor destruction in the adult zebrafish retina...
October 2013: Glia
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