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

作者：S****kumar Rajendran; Indulekha Chandrasekharan Lalitha; Divya Thulasi Sheela; Divya Mundackal Sivaraman; Anto Ruby John; Vinod Balachandran; Vidyanand Sasidharan; Jagatha Balusamy; Venugopal Shalini; James Jackson^*

来源：Journal of Neurochemistry, 2010, 113(4): 807-818.

DOI：10.1111/j.1471-4159.2010.06574.x

• embryonic stem cells
• FGF2
• Hes-1
• JNK signaling
• neural progenitors
• notch signaling
• proliferation

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.

• 出版日期2010-5