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

Abstract

J. Neurochem. (2010) 113, 807–818. 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.

JNK1 Inhibits GluR1 Expression and GluR1-Mediated Calcium Influx through Phosphorylation and Stabilization of Hes-1

“…Thus, Hes-1 may be a common substrate of the JNK kinase family in neurons. This speculation is consistent with the report that bFGF2 enhances Hes-1 expression through direct binding of JNK-activating transcription factor 2 (ATF2) to the Hes-1 promoter (Sanalkumar et al, 2010), whereas ATF2 is a downstream target of JNK (Gupta et al, 1995). Moreover, Hes-1 suppression of GluR1 expression decreased calcium influx upon AMPA stimulation in cortical neurons.…”

Notch-mediated patterning and cell fate allocation of pancreatic progenitor cells

“…Whereas early stage Hes1-positive cells were observed to be multipotent, later stage Hes1-positive cells were restricted to the duct and acinar lineages (Kopinke et al, 2011). The implication of this for the role of Notch signaling in endocrine/duct fate patterning versus a specific role of Hes1 in late stage acinar cell progenitors is not yet clear, and might be rooted in Notch-independent control of Hes1 expression (Curry et al, 2006;Ingram et al, 2008;Nakayama et al, 2008;Sanalkumar et al, 2010;Wall et al, 2009), or a later role for Notch/Hes1 within the centroacinar cell type, which is not yet fully formed at the secondary transition. Further evidence for the suppressive effect of Notch signaling on the acinar fate is derived from the inhibitory effect of Notch on the transcriptional activity of the pro-acinar factor Ptf1a (Esni et al, 2004).…”

Adiponectin Stimulates Proliferation of Adult Hippocampal Neural Stem/Progenitor Cells through Activation of p38 Mitogen-activated Protein Kinase (p38MAPK)/Glycogen Synthase Kinase 3β (GSK-3β)/β-Catenin Signaling Cascade

“…Recent studies have reported that ERK1/2 activation is involved in regulating proliferation of adult hNSCs (58 -60). JNK signaling has been shown to mediate FGF2-stimulated proliferation of embryonic neural stem cells (61). JNK signaling is also involved in differentiation and apoptosis of neural stem cells (62)(63)(64).…”