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Search results for: Ascl1a (zebrafish)

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#32004993   2020/01/07 To Up

Biphasic Role of Tgf-β Signaling during Müller Glia Reprogramming and Retinal Regeneration in Zebrafish.

Tgf-β signaling is a major antiproliferative pathway governing different biological functions, including cellular reprogramming. Upon injury, Müller glial cells of zebrafish retina reprogram to form progenitors (MGPCs) essential for regeneration. Here, the significance of Tgf-β signaling for inducing MGPCs is explored. Notably, Tgf-β signaling not only performs a pro-proliferative function but also is necessary for the expression of several regeneration-associated, essential transcription factor genes such as ascl1a, lin28a, oct4, sox2, and zebs and various microRNAs, namely, miR-200a, miR-200b, miR-143, and miR-145 during different phases of retinal regeneration. This study also found the indispensable role played by Mmp2/Mmp9 in the efficacy of Tgf-β signaling. Furthermore, the Tgf-β signaling is essential to cause cell cycle exit of MGPCs towards later phases of regeneration. Finally, the Delta-Notch signaling in collaboration with Tgf-β signaling regulates the critical factor, Her4.1. This study provides novel insights into the biphasic roles of Tgf-β signaling in zebrafish during retinal regeneration.
Poonam Sharma, Shivangi Gupta, Mansi Chaudhary, Soumitra Mitra, Bindia Chawla, Mohammad Anwar Khursheed, Navnoor Kaur Saran, Rajesh Ramachandran

1839 related Products with: Biphasic Role of Tgf-β Signaling during Müller Glia Reprogramming and Retinal Regeneration in Zebrafish.

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#31444939   2019/08/24 To Up

Inflammation-induced mammalian target of rapamycin signaling is essential for retina regeneration.

Upon retina injury, Müller glia in the zebrafish retina respond by generating multipotent progenitors to repair the retina. However, the complete mechanisms underlying retina regeneration remain elusive. Here we report inflammation-induced mammalian target of rapamycin (mTOR) signaling in the Müller glia is essential for retina regeneration in adult zebrafish. We show after a stab injury, mTOR is rapidly activated in Müller glia and later Müller glia-derived progenitor cells (MGPCs). Importantly, mTOR is required for Müller glia dedifferentiation, as well as the proliferation of Müller glia and MGPCs. Interestingly, transient mTOR inhibition by rapamycin only reversibly suppresses MGPC proliferation, while its longer suppression by knocking down Raptor significantly inhibits the regeneration of retinal neurons. We further show mTOR promotes retina regeneration by regulating the mRNA expression of key reprogramming factors ascl1a and lin-28a, cell cycle-related genes and critical cytokines. Surprisingly, we identify microglia/macrophage-mediated inflammation as an important upstream regulator of mTOR in the Müller glia and it promotes retina regeneration through mTOR. Our study not only demonstrates the important functions of mTOR but also reveals an interesting link between inflammation and the mTOR signaling during retina regeneration.
Zhiqiang Zhang, Haitao Hou, Shuguang Yu, Cuiping Zhou, Xiaoli Zhang, Na Li, Shuqiang Zhang, Kaida Song, Ying Lu, Dong Liu, Hong Lu, Hui Xu

1277 related Products with: Inflammation-induced mammalian target of rapamycin signaling is essential for retina regeneration.

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#30606747   2019/01/03 To Up

Dual regulation of by Myc is necessary during zebrafish retina regeneration.

Cellular reprogramming leading to induction of Muller glia-derived progenitor cells (MGPCs) with stem cell characteristics is essential for zebrafish retina regeneration. Although several regeneration-specific genes are characterized, the significance of MGPC-associated Mycb induction remains unknown. Here, we show that early expression of Mycb induces expression of genes like , a known activator of in MGPCs. Notably, is simultaneously activated by Ascl1a and repressed by Insm1a in regenerating retina. Here, we unravel a dual role of Mycb in expression, both as an activator through Ascl1a in MGPCs and a repressor in combination with Hdac1 in neighboring cells. Myc inhibition reduces the number of MGPCs and abolishes normal regeneration. Myc in collaboration with Hdac1 inhibits , an effector of Delta-Notch signaling. Further, we also show the repressive role of Delta-Notch signaling on expression in post-injured retina. Our studies reveal mechanistic understanding of Myc pathway during zebrafish retina regeneration, which could pave way for therapeutic intervention during mammalian retina regeneration.
Soumitra Mitra, Poonam Sharma, Simran Kaur, Mohammad Anwar Khursheed, Shivangi Gupta, Mansi Chaudhary, Akshai J Kurup, Rajesh Ramachandran

1856 related Products with: Dual regulation of by Myc is necessary during zebrafish retina regeneration.

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#30577041   // To Up

Granulin 1 Promotes Retinal Regeneration in Zebrafish.

Retinal degenerative diseases can progress to severe reductions of vision. In general, the changes are permanent in higher vertebrates, including humans; however, retinal regeneration can occur in lower vertebrates, such as amphibians and teleost fish. Progranulin is a secreted growth factor that is involved in normal development and wound-healing processes. We have shown that progranulin promotes the proliferation of retinal precursor cells in mouse retinas. The purpose of this study was to investigate the role played by granulin 1 (grn1) in the retinal regeneration in zebrafish.
Kazuhiro Tsuruma, Yuichi Saito, Hiroyuki Okuyoshi, Akihiro Yamaguchi, Masamitsu Shimazawa, Daniel Goldman, Hideaki Hara

1231 related Products with: Granulin 1 Promotes Retinal Regeneration in Zebrafish.

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#30267687   2018/08/16 To Up

Histone Deacetylase-Mediated Müller Glia Reprogramming through Her4.1-Lin28a Axis Is Essential for Retina Regeneration in Zebrafish.

Histone deacetylases (Hdacs) play significant roles in cellular homeostasis and tissue differentiation. Hdacs are well characterized in various systems for their physiological and epigenetic relevance. However, their significance during retina regeneration remains unclear. Here we show that inhibition of Hdac1 causes a decline in regenerative ability, and injury-dependent regulation of hdacs is essential for regulating regeneration-associated genes like ascl1a, lin28a, and repressors like her4.1 at the injury site. We show selective seclusion of Hdac1 from the proliferating Müller glia-derived progenitor cells (MGPCs) and its upregulation in the neighboring cells. Hdacs negatively regulate her4.1, which also represses lin28a and essential cytokines to control MGPCs proliferation. Interestingly, Hdacs' inhibition reversibly blocks regeneration through the repression of critical cytokines and other regeneration-specific genes, which is also revealed by whole-retina RNA sequence analysis. Our study shows mechanistic understanding of the Hdac pathway during zebrafish retina regeneration.
Soumitra Mitra, Poonam Sharma, Simran Kaur, Mohammad Anwar Khursheed, Shivangi Gupta, Riya Ahuja, Akshai J Kurup, Mansi Chaudhary, Rajesh Ramachandran

2809 related Products with: Histone Deacetylase-Mediated Müller Glia Reprogramming through Her4.1-Lin28a Axis Is Essential for Retina Regeneration in Zebrafish.

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#30077009   2018/08/01 To Up

Spatiotemporal control of zebrafish (Danio rerio) gene expression using a light-activated CRISPR activation system.

CRISPR activation (CRISPRa) system is the convenient tool for targeted-gene activation, it has been developed and combined with a lighting-based system that can control transcription initiation spatially and temporally by utilizing photoreceptor derived from plant Arabidopsis thaliana. A blue light photoreceptor the Cryptochrome 2 (CRY2), and its binding partner CIB1 will dimerize by exposure to the blue light and it has been applied to human cells. However, the application of a combination of these two systems to zebrafish cell is still not explored. We performed zebrafish gene activation using p65 and VP64 activators in the zebrafish cells (ZF4). Our study demonstrated that we have successfully controlled the transcription level of ASCL1a, BCL6a, and HSP70 genes using blue light-activated CRISPR activation system. The result showed that using this system, mRNA level expression of ASCL1a, BCL6a, and HSP70 genes increased after irradiated under blue light for several hours and significantly different to those which treated in the dark.
Rizka Rahmana Putri, Liangbiao Chen

2335 related Products with: Spatiotemporal control of zebrafish (Danio rerio) gene expression using a light-activated CRISPR activation system.

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#29719254   // To Up

let-7 MicroRNA-Mediated Regulation of Shh Signaling and the Gene Regulatory Network Is Essential for Retina Regeneration.

Upon injury, Müller glia cells of the zebrafish retina reprogram themselves to progenitor cells with stem cell characteristics. This necessity for retina regeneration is often compromised in mammals. We explored the significance of developmentally inevitable Sonic hedgehog signaling and found its necessity in MG reprogramming during retina regeneration. We report on stringent translational regulation of sonic hedgehog, smoothened, and patched1 by let-7 microRNA, which is regulated by Lin28a, in Müller glia (MG)-derived progenitor cells (MGPCs). We also show Shh-signaling-mediated induction of Ascl1 in mouse and zebrafish retina. Moreover, Shh-signaling-dependent regulation of matrix metalloproteinase9, in turn, regulates Shha levels and genes essential for retina regeneration, such as lin28a, zic2b, and foxn4. These observations were further confirmed through whole-retina RNA-sequencing (RNA-seq) analysis. This mechanistic gene expression network could lead to a better understanding of retina regeneration and, consequently, aid in designing strategies for therapeutic intervention in human retinal diseases.
Simran Kaur, Shivangi Gupta, Mansi Chaudhary, Mohammad Anwar Khursheed, Soumitra Mitra, Akshai Janardhana Kurup, Rajesh Ramachandran

1289 related Products with: let-7 MicroRNA-Mediated Regulation of Shh Signaling and the Gene Regulatory Network Is Essential for Retina Regeneration.

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