<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>
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.