Impaired caudal fin‐fold regeneration in zebrafish deficient for the tumor suppressor Pten

Hale, Alexander James; Kiai, Ali; Sikkens, Jelte; Hertog, Jeroen den

doi:10.1002/reg2.88

Cited by 11 publications

(8 citation statements)

References 40 publications

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“…22 Disruption in any of these pathways could adversely alter the regenerative capacity of zebrafish caudal fin. [40][41][42] Based on our data, we propose that basp1 regulates revascularization through the Wnt/β-catenin pathway and accompanied pathways such as notch signaling. Further studies to elucidate how BASP1 modulates CXXC4, an epigenetic silencer of the β-catenin gene, expression will provide valuable new information in understanding the direct role of BASP1 in angiogenic responsiveness.…”

Section: F I G U R Ementioning

confidence: 94%

Identification of Basp1 as a novel angiogenesis‐regulating gene by multi‐model system studies

et al. 2021

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We have previously used the genetic diversity available in common inbred mouse strains to identify quantitative trait loci (QTLs) responsible for the differences in angiogenic response using the corneal micropocket neovascularization (CoNV) assay.Employing a mouse genome-wide association study (GWAS) approach, the region on chromosome 15 containing Basp1 was identified as being significantly associated with angiogenesis in inbred strains. Here, we developed a unique strategy to determine and verify the role of BASP1 in angiogenic pathways. Basp1 expression in cornea had a strong correlation with a haplotype shared by mouse strains with varied angiogenic phenotypes. In addition, inhibition of BASP1 demonstrated a dosagedependent effect in both primary mouse brain endothelial and human microvascular endothelial cell (HMVEC) migration. To investigate its role in vivo, we knocked out basp1 in transgenic kdrl:zsGreen zebrafish embryos using a widely adopted CRISPR-Cas9 system. These embryos had severely disrupted vessel formation compared to control siblings. We further show that basp1 promotes angiogenesis by upregulating β-catenin gene and the Dll4/Notch1 signaling pathway. These results, to the best of our knowledge, provide the first in vivo evidence to indicate the role of Basp1 as an angiogenesis-regulating gene and opens the potential therapeutic avenues for a wide variety of systemic angiogenesis-dependent diseases. K E Y W O R D Sangiogenesis, basic fibroblast growth factor (bFGF), brain abundant membrane attached signal protein 1 (BASP1), corneal micropocket neovascularization (CoNV), efficient mixed model association (EMMA), genome-wide association (GWAS), Wilm's tumor (WT1), Wnt/β-catenin pathway 2 of 15 | KHAJAVI et Al.

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Section: F I G U R Ementioning

confidence: 94%

Identification of Basp1 as a novel angiogenesis‐regulating gene by multi‐model system studies

et al. 2021

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“…Another miRNA, miR-21, could decrease autophagy by down-regulating PTEN in mesangial cells [ 37 ]. In fish, it has been reported that zebrafish PTEN deficiency induced the activation of PI3K/mTOR pathway and AKT, which affected embryo and tissue development [ 38 , 41 ]; madaka PTEN knockout also upregulated PI3K/AKT signaling, which led to abnormal embryo development [ 42 ]. In the present study, we found that compared with human and mouse PTEN, fish PTEN homologs are highly conserved in sequence and structure, and, in flounder, PoPTEN was constitutively expressed in a wide range of tissues.…”

Section: Discussionmentioning

confidence: 99%

“…In mammals, it has been demonstrated that miRNAs regulate cell apoptosis, proliferation, and autophagy by targeting PTEN [ 35 , 36 , 37 ]. In fish, studies on PTEN have been documented mainly in zebrafish, in which it was shown that PTEN played an important role in embryonic development, caudal fin-fold regeneration, tumorigenesis, hematopoiesis, and myelocyte migration [ 38 , 39 , 40 , 41 ]. In medaka, PTEN was also shown to be involved in embryo development [ 42 ].…”

Section: Introductionmentioning

confidence: 99%

Phosphatase and Tensin Homolog (PTEN) of Japanese Flounder—Its Regulation by miRNA and Role in Autophagy, Apoptosis and Pathogen Infection

Guan

Sun

2020

IJMS

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MicroRNAs (miRNAs) are small non-coding RNAs with important roles in diverse biological processes including immunity. Japanese flounder (Paralichthys olivaceus) is an aquaculture fish species susceptible to the infection of bacterial and viral pathogens including Edwardsiella tarda. In a previous study, pol-miR-novel_547, a novel miRNA of flounder with unknown function, was found to be induced by E. tarda. In the present study, we investigated the regulation and function of pol-miR-novel_547 and its target gene. We found that pol-miR-novel_547 was regulated differently by E. tarda and the viral pathogen megalocytivirus, and pol-miR-novel_547 repressed the expression of PTEN (phosphatase and tensin homolog) of flounder (PoPTEN). PoPTEN is ubiquitously expressed in multiple tissues of flounder and responded to bacterial and viral infections. Interference with PoPTEN expression in flounder cells directly or via pol-miR-novel_547 promoted E. tarda invasion. Consistently, in vivo knockdown of PoPTEN enhanced E. tarda dissemination in flounder tissues, whereas in vivo overexpression of PoPTEN attenuated E. tarda dissemination but facilitated megalocytivirus replication. Further in vitro and in vivo studies showed that PoPTEN affected autophagy activation via the AKT/mTOR pathway and also modulated the process of apoptosis. Together these results reveal for the first time a critical role of fish PTEN and its regulatory miRNA in pathogen infection, autophagy, and apoptosis.

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“…One study conducted by the Jazwinska group revealed that the activity of bone morphogenetic protein (BMP) is responsible for WE maintenance and osteoblast and blood vessel formation (Thorimbert et al, 2015). Moreover, it has been observed that the phosphatase and tumor suppressor Pten, which is an antagonist of phosphoinositide-3-kinase (PI3K) signaling, is required for caudal fin fold regeneration in zebrafish larvae (Hale et al, 2017). A recent study found that homozygous knockout mutant zebrafish embryos lacking functional Pten (ptena −/− ptenb −/− ) were not capable of regenerating their caudal fin folds.…”

Section: Zebrafish and Tail Fin Regenerationmentioning

confidence: 99%

“…These organisms showed decreased proliferation and enhanced apoptotic activity. The reinduction of Pten expression or pharmacological inhibition of PI3K, in turn, rescued the regenerative process (Hale et al, 2017). In addition to proliferative cells from the blastema, several studies have shown that macrophages play an important role in regenerative processes through protein synthesis, angiogenesis, the production and release of cytokines such as VEGF and interleukin 1 (IL-1), and the promotion of cell proliferation (Koh and DiPietro, 2011; Wynn and Vannella, 2016; Godwin et al, 2017; Abnave and Ghigo, 2018).…”

Section: Zebrafish and Tail Fin Regenerationmentioning

confidence: 99%

Understanding the Metabolic Profile of Macrophages During the Regenerative Process in Zebrafish

2019

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In contrast to mammals, lower vertebrates, including zebrafish (Danio rerio), have the ability to regenerate damaged or lost tissues, such as the caudal fin, which makes them an ideal model for tissue and organ regeneration studies. Since several diseases involve the process of transition between fibrosis and tissue regeneration, it is necessary to attain a better understanding of these processes. It is known that the cells of the immune system, especially macrophages, play essential roles in regeneration by participating in the removal of cellular debris, release of pro-and anti-inflammatory factors, remodeling of components of the extracellular matrix and alteration of oxidative patterns during proliferation and angiogenesis. Immune cells undergo phenotypical and functional alterations throughout the healing process due to growth factors and cytokines that are produced in the tissue microenvironment. However, some aspects of the molecular mechanisms through which macrophages orchestrate the formation and regeneration of the blastema remain unclear. In the present review, we outline how macrophages orchestrate the regenerative process in zebrafish and give special attention to the redox balance in the context of tail regeneration.

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Impaired caudal fin‐fold regeneration in zebrafish deficient for the tumor suppressor Pten

Cited by 11 publications

References 40 publications

Identification of Basp1 as a novel angiogenesis‐regulating gene by multi‐model system studies

Identification of Basp1 as a novel angiogenesis‐regulating gene by multi‐model system studies

Phosphatase and Tensin Homolog (PTEN) of Japanese Flounder—Its Regulation by miRNA and Role in Autophagy, Apoptosis and Pathogen Infection

Understanding the Metabolic Profile of Macrophages During the Regenerative Process in Zebrafish

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