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Publication Type : Journal Article
Publisher : J Neurochem
Source : J Neurochem, Volume 113, Issue 4, p.807-18 (2010)
Keywords : activating transcription factor 2, Animals, Basic Helix-Loop-Helix Transcription Factors, cell differentiation, Cell Line, central nervous system, Fibroblast Growth Factor 2, Gene Expression Regulation, Developmental, Homeodomain Proteins, Immunoglobulin J Recombination Signal Sequence-Binding Protein, JNK Mitogen-Activated Protein Kinases, Mice, Neurons, Promoter Regions, Genetic, Receptors, Notch, signal transduction, Stem cells, Transcription Factor HES-1, Transcriptional Activation
Campus : Amritapuri
School : School of Biotechnology
Department : biotechnology
Year : 2010
Abstract : Hes-1 and Hes-5 are downstream effectors of Notch signaling that are known to be involved in different aspects of neural stem cell proliferation and differentiation. Evidence has emerged that Hes-1 expression can be regulated by alternate signaling pathways independent of canonical Notch/CBF1 interaction. This context-dependent differential regulation of Hes-1 expression in neural progenitor gains a lot of importance as it would help in its exponential expansion without the requirement of interaction from neighboring cells during development. Here, we have clearly demonstrated the existence of a population of neural progenitors with Notch/CBF1-independent Hes-1 expression in vitro. Further analysis demonstrated the role of FGF2 in activating Hes-1 expression through the direct binding of ATF2, a JNK downstream target, on Hes-1 promoter. This raises the possibility for the existence of two distinct populations of neural progenitors - one maintained by Hes-1 expression exclusively through Notch-independent mechanism and the other mediating Hes-1 expression through both canonical Notch and FGF2-ATF2 pathway. This alternative pathway will insure a constant expression of Hes-1 even in the absence of canonical Notch intracellular domain-mediated signaling, thereby maintaining a pool of proliferating neural progenitors required during development.
Cite this Research Publication : Rajendran Sanalkumar, Indulekha C. L. Pillai, Thulasi Sheela Divya, Mundackal Sivaraman Divya, Anto Ruby John, Balachandran Vinod, Sasidharan Vidyanand, Balusamy Jagatha, Shalini Venugopal, and Jackson James, “ATF2 maintains a subset of neural progenitors through CBF1/Notch independent Hes-1 expression and synergistically activates the expression of Hes-1 in Notch-dependent neural progenitors.”, J Neurochem, vol. 113, no. 4, pp. 807-18, 2010.