Myc regulates programmed cell death and radial glia dedifferentiation after neural injury in an echinoderm

BMC Developmental Biology

José E García-Arrarás¹  Olga R Zueva¹  Vladimir S Mashanov¹ 

[1]University of Puerto Rico, Rio Piedras, PO Box 70377, San Juan, PR 00936-8377, USA

关键词: Cell death;    Dedifferentiation;    Central nervous system;    Regeneration;    Myc;   

Others  :  1209033
DOI  :  10.1186/s12861-015-0071-z

 received in 2015-02-20, accepted in 2015-05-01,  发布年份 2015

【 摘 要 】

Background

Adult echinoderms can completely regenerate major parts of their central nervous system even after severe injuries. Even though this capacity has long been known, the molecular mechanisms that drive fast and complete regeneration in these animals have remained uninvestigated. The major obstacle for understanding these molecular pathways has been the lack of functional genomic studies on regenerating adult echinoderms.

Results

Here, we employ RNA interference-mediated gene knockdown to characterize the role of Myc during the early (first 48 hours) post-injury response in the radial nerve cord of the sea cucumber Holothuria glaberrima. Our previous experiments identified Myc as the only pluripotency-associated factor, whose expression significantly increased in the wounded CNS. The specific function(s) of this gene, however, remained unknown. Here we demonstrate that knockdown of Myc inhibits dedifferentiation of radial glia and programmed cell death, the two most prominent cellular events that take place in the regenerating sea cucumber nervous system shortly after injury.

Conclusions

In this study, we show that Myc overexpression is required for proper dedifferentiation of radial glial cells and for triggering the programmed cell death in the vicinity of the injury. Myc is thus the first transcription factor, whose functional role has been experimentally established in echinoderm regeneration.

【 授权许可】

   
2015 Mashanov et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]Mashanov VS, Zueva OR, Heinzeller T. Regeneration of the radial nerve cord in a holothurian: a promising new model system for studying post-traumatic recovery in the adult nervous system. Tissue Cell. 2008; 40(5):351-72.
• [2]San Miguel-Ruiz JE, García-Arrarás JE. Common cellular events occur during wound healing and organ regeneration in the sea cucumber Holothuria glaberrima. BMC Dev Biol. 2007; 7:115.
• [3]Mashanov VS, Zueva OR, García-Arrarás JE. Radial glial cells play a key role in echinoderm neural regeneration. BMC Biology. 2013; 11(1):49. BioMed Central Full Text
• [4]Karimi-Abdolrezaee S, Billakanti R. Reactive astrogliosis after spinal cord injury-beneficial and detrimental effects. Mol Neurobiol. 2012; 46(2):251-64.
• [5]Cregg JM, DePaul MA, Filous AR, Lang BT, Tran A, Silver J. Functional regeneration beyond the glial scar. Exp Neurol. 2014; 253:197-207.
• [6]Mashanov VS, Zueva OR, García-Arrarás JE. Transcriptomic changes during regeneration of the central nervous system in an echinoderm. BMC Genomics. 2014; 15(1):357.
• [7]Mashanov VS, Zueva OR, García-Arrarás JE. Expression of pluripotency factors in echinoderm regeneration. Cell Tissue Res. 2014. in press doi:10.1007/s00441-014-2040-4.
• [8]Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76.
• [9]Maki N, Suetsugu-Maki R, Tarui H, Agata K, Del Rio-Tsonis K, Tsonis PA. Expression of stem cell pluripotency factors during regeneration in newts. Dev Dyn. 2009; 238(6):1613-1616.
• [10]Christen B, Robles V, Raya M, Paramonov I, Izpisúa Belmonte JC. Regeneration and reprogramming compared. BMC Biol. 2010; 8:5.
• [11]Murphy MJ, Wilson A, Trumpp A. More than just proliferation: Myc function in stem cells. Trends Cell Biol. 2005; 15(3):128-37.
• [12]Dang CV, O’Donnell KA, Zeller KI, Nguyen T, Osthus RC, Li F. The c-myc target gene network. Semin Cancer Biol. 2006; 16(4):253-64.
• [13]Knoepfler PS. Why myc? an unexpected ingredient in the stem cell cocktail. Cell Stem Cell. 2008; 2(1):18-21.
• [14]Meyer N, Penn LZ. Reflecting on 25 years with MYC,. Nat Rev Cancer. 2008; 8(12):976-90.
• [15]Kim DH, Behlke MA, Rose SD, Chang MS, Choi S, Rossi JJ. Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy. Nat Biotechnol. 2005; 23(2):222-6.
• [16]Mashanov V, Zueva O, Heinzeller T, Dolmatov I. Ultrastructure of the circumoral nerve ring and the radial nerve cords in holothurians (Echinodermata). Zoomorphology. 2006; 125(1):27-38.
• [17]Mashanov VS, Zueva OR, Garcia-Arraras JE. Organization of glial cells in the adult sea cucumber central nervous system. Glia. 2010; 58(13):1581-1593.
• [18]Gatti G, Maresca G, Natoli M, Florenzano F, Nicolin A, Felsani A et al.. MYC prevents apoptosis and enhances endoreduplication induced by paclitaxel. PLoS One. 2009; 4(5):5442.
• [19]Fernandez PC, Frank SR, Wang L, Schroeder M, Liu S, Greene J et al.. Genomic targets of the human c-myc protein. Genes Dev. 2003; 17(9):1115-1129.
• [20]Hasegawa K, Chang YW, Li H, Berlin Y, Ikeda O, Kane-Goldsmith N et al.. Embryonic radial glia bridge spinal cord lesions and promote functional recovery following spinal cord injury. Exp Neurol. 2005; 193(2):394-410.
• [21]Chera S, Ghila L, Dobretz K, Wenger Y, Bauer C, Buzgariu W et al.. Apoptotic cells provide an unexpected source of Wnt3 signaling to drive Hydra head regeneration. Dev Cell. 2009; 17(2):279-89.
• [22]Tseng AS, Adams DS, Qiu D, Koustubhan P, Levin M. Apoptosis is required during early stages of tail regeneration in Xenopus laevis. Dev Biol. 2007; 301(1):62-9.
• [23]Naito Y, Ui-Tei K. siRNA design software for a target gene-specific RNA interference. Front Genet. 2012; 3:102.
• [24]Integrated DNA Technologies. Dicer Substrate RNAi Design. 2005. http://www.idtdna.com/pages/docs/default-source/technical-reports/DicerDesignRules.pdf?sfvrsn=1.
• [25]Holmes K, Williams CM, Chapman EA, Cross MJ. Detection of siRNA induced mRNA silencing by RT-qPCR: considerations for experimental design. BMC Res Notes. 2010; 3:53.
• [26]Matz MV, Wright RM, Scott JG. No control genes required: Bayesian analysis of qRT-PCR data. PLoS One. 2013; 8(8):71448.
• [27]R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria; 2014.
• [28]Mashanov VS, Zueva OR, García-Arrarás JE. Posttraumatic regeneration involves differential expression of long terminal repeat (LTR) retrotransposons. Dev Dyn. 2012; 241(10):1625-1636.