scholarly journals A Cut/cohesin axis alters the chromatin landscape to facilitate neuroblast death

2018 ◽  
Author(s):  
Richa Arya ◽  
Seda Gyonjyan ◽  
Katherine Harding ◽  
Tatevik Sarkissian ◽  
Ying Li ◽  
...  

AbstractPrecise control of cell death in the nervous system is essential for development. Spatial and temporal factors activate the death of Drosophila neural stem cells (neuroblasts) by controlling the transcription of multiple cell death genes through a shared enhancer, enh1. The activity of enh1 is controlled by abdominalA and Notch, but additional inputs are needed for proper specificity. Here we show that the Cut DNA binding protein is required for neuroblast death, acting downstream of enh1. In the nervous system, Cut promotes an open chromatin conformation in the cell death gene locus, allowing cell death gene expression in response to abdominalA. We demonstrate a temporal increase in global H3K27me3 levels in neuroblasts, which is enhanced by cut knockdown. Furthermore, cut regulates the expression of the cohesin subunit Stromalin in the nervous system. The cohesin components Stromalin and NippedB are required for neuroblast death, and knockdown of Stromalin increases repressive histone modifications in neuroblasts. Thus Cut and cohesin regulate apoptosis in the developing nervous system by altering the chromatin landscape.Summary statementCut regulates the programmed death of neural stem cells by altering cohesin levels and promoting a more open chromatin conformation to allow cell death gene expression.

Author(s):  
Prithiv K R Kumar

Stem cells have the capacity to differentiate into any type of cell or organ. Stems cell originate from any part of the body, including the brain. Brain cells or rather neural stem cells have the capacitive advantage of differentiating into the central nervous system leading to the formation of neurons and glial cells. Neural stem cells should have a source by editing DNA, or by mixings chemical enzymes of iPSCs. By this method, a limitless number of neuron stem cells can be obtained. Increase in supply of NSCs help in repairing glial cells which in-turn heal the central nervous system. Generally, brain injuries cause motor and sensory deficits leading to stroke. With all trials from novel therapeutic methods to enhanced rehabilitation time, the economy and quality of life is suppressed. Only PSCs have proven effective for grafting cells into NSCs. Neurons derived from stem cells is the only challenge that limits in-vitro usage in the near future.


2003 ◽  
Vol 144 ◽  
pp. s11 ◽  
Author(s):  
S. Ceccatelli ◽  
C. Tamm ◽  
E. Sleeper ◽  
S. Orrenius ◽  
E.Y. Snyder

Stem Cells ◽  
2011 ◽  
Vol 29 (11) ◽  
pp. 1817-1828 ◽  
Author(s):  
Toshiyuki Ohtsuka ◽  
Hiromi Shimojo ◽  
Mitsuhiro Matsunaga ◽  
Naoki Watanabe ◽  
Kohei Kometani ◽  
...  

RSC Advances ◽  
2017 ◽  
Vol 7 (65) ◽  
pp. 41098-41104 ◽  
Author(s):  
Ruirui Yang ◽  
Caixia Xu ◽  
Tao Wang ◽  
Yuanqi Wang ◽  
Jingnan Wang ◽  
...  

The enhancement of the biological properties of hydrogels by surface modifying with bioactive molecules is of great significance, especially for the treatment of central nervous system injury by combining engrafted cells.


2017 ◽  
Vol 125 (4) ◽  
pp. 721-729 ◽  
Author(s):  
Peter J. Wagner ◽  
Hae-Ryung Park ◽  
Zhaoxi Wang ◽  
Rory Kirchner ◽  
Yongyue Wei ◽  
...  

Author(s):  
Ram Wagle ◽  
Young-Han Song

Abstract Background Cranial radiation therapy for treating childhood malignancies in the central nervous system or accidental radiation exposure may result in neurological side effects in surviving adults. As tissue homeostasis is maintained by stem cells, understanding the effect of radiation on neural stem cells will provide clues for managing the neurological effects. Drosophila embryos were used as a model system whose sensitivity to irradiation-induced cell death changes from the sensitive to resistant stage during development. Objective Drosophila embryos at the radiation-sensitive stage were irradiated at various doses and the radiation sensitivity was tested regarding the appearance of apoptotic cells in the embryos and the embryonic lethality. Cell fates of the neural stem cells called neuroblasts (NBs) and adult motor function after irradiation were also investigated. Result Irradiation of Drosophila embryos at the radiation-sensitive stage resulted in a dose-dependent increase in the number of embryos containing apoptotic cells 75 min after treatment starting at 3 Gy. Embryonic lethality assayed by hatch rate was induced by 1 Gy irradiation, which did not induce cell death. Notably, no apoptosis was detected in NBs up to 2 h after irradiation at doses as high as 40 Gy. At 3 h after irradiation, as low as 3 Gy, the number of NBs marked by Dpn and Klu was decreased by an unidentified mechanism regardless of the cell death status of the embryo. Furthermore, embryonic irradiation at 3 Gy, but not 1 Gy, resulted in locomotor defects in surviving adults. Conclusion Embryonic NBs survived irradiation at doses as high as 40 Gy, while cells in other parts of the embryos underwent apoptosis at doses higher than 3 Gy within 2 h after treatment. Three hours after exposure to a minimum dose of 3 Gy, the number of NBs marked by Dpn and Klu decreased, and the surviving adults exhibited defects in locomotor ability.


Author(s):  
Srivathsa S. Magadi ◽  
Chrysanthi Voutyraki ◽  
Gerasimos Anagnostopoulos ◽  
Evanthia Zacharioudaki ◽  
Ioanna K. Poutakidou ◽  
...  

ABSTRACTNeural stem cells divide during embryogenesis and post embryonic development to generate the entire complement of neurons and glia in the nervous system of vertebrates and invertebrates. Studies of the mechanisms controlling the fine balance between neural stem cells and more differentiated progenitors have shown that in every asymmetric cell division progenitors send a Delta-Notch signal back to their sibling stem cells. Here we show that excessive activation of Notch or overexpression of its direct targets of the Hes family causes stem-cell hyperplasias in the Drosophila larval central nervous system, which can progress to malignant tumours after allografting to adult hosts. We combined transcriptomic data from these hyperplasias with chromatin occupancy data for Dpn, a Hes transcription factor, to identify genes regulated by Hes factors in this process. We show that the Notch/Hes axis represses a cohort of transcription factor genes. These are excluded from the stem cells and promote early differentiation steps, most likely by preventing the reversion of immature progenitors to a stem-cell fate. Our results suggest that Notch signalling sets up a network of mutually repressing stemness and anti-stemness transcription factors, which include Hes proteins and Zfh1, respectively. This mutual repression ensures robust transition to neuronal and glial differentiation and its perturbation can lead to malignant transformation.


2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Anthony M. Rossi ◽  
Shadi Jafari ◽  
Claude Desplan

During the approximately 5 days of Drosophila neurogenesis (late embryogenesis to the beginning of pupation), a limited number of neural stem cells produce approximately 200,000 neurons comprising hundreds of cell types. To build a functional nervous system, neuronal types need to be produced in the proper places, appropriate numbers, and correct times. We discuss how neural stem cells (neuroblasts) obtain so-called area codes for their positions in the nervous system (spatial patterning) and how they keep time to sequentially produce neurons with unique fates (temporal patterning). We focus on specific examples that demonstrate how a relatively simple patterning system (Notch) can be used reiteratively to generate different neuronal types. We also speculate on how different modes of temporal patterning that operate over short versus long time periods might be linked. We end by discussing how specification programs are integrated and lead to the terminal features of different neuronal types. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


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