Publication Type:

Journal Article


J Neurochem, Volume 113, Issue 4, p.807-18 (2010)



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


<p>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.</p>

Cite this Research Publication

R. Sanalkumar, Dr. Indulekha C. L. Pillai, Divya, T. Sheela, Divya, M. Sivaraman, Anto, R. John, Vinod, B., Vidyanand, S., Jagatha, B., Venugopal, S., and James, J., “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.